The Role of CD40 in Allergic Rhinitis and Airway Remodelling

Background. Allergic rhinitis (AR) affects millions of people and is lack of effective treatment. CD40 is an important costimulatory molecule in immunity. However, few studies have focused on the role of CD40 in AR. Methods. In this study, we built mouse model of chronic AR. The mice were divided into the AR, control, intravenous CD40 siRNA, and nasal CD40 siRNA groups ( n = 6 each). We detected OVA-sIgE, IL-4, IL-5, IL-13, IL-10, IFN-γ, and TGF-β levels in serum and supernatant by ELISA, CD40+ splenic DCs, and Foxp3+ Tregs by flow cytometry and CD40 mRNA by RT2-PCR. We also used PAS and MT stains to assess tissue remodelling. Results. (1) The OVA-sIgE, IL-4, IL-5, and IL-13 levels in the serum or supernatant of nasal septal membrane of AR mice were significantly higher than control. After treated with CD40 siRNA, those indicators were significantly decreased. The IFN-γ, IL-10, and TGF-β levels in AR mice were significantly lower than that in control and were increased by administration of CD40 siRNA. (2) AR mice had significantly fewer Foxp3+ Tregs in the spleen than control mice. After treated with CD40 siRNA, AR mice had significantly more Foxp3+ Tregs. (3) AR mice exhibited a significantly higher CD40 mRNA levels than control. Administration of CD40 siRNA significantly reduced the CD40 mRNA level. (4) The AR mice showed significantly greater collagen deposition than the control in MT staining. Applications of CD40 siRNA significantly reduced the collagen deposition in AR mice. Conclusion. CD40 siRNA therapy shows promise for chronic AR as it significantly attenuated allergic symptoms and Th2-related inflammation and upregulated Foxp3+ Tregs. CD40 plays a role in tissue remodelling in AR, which can be inhibited by CD40 siRNA application.

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PGC-1α is associated with C2C12 Myoblast differentiation

Open Life Sciences ◽

10.2478/s11535-014-0341-y ◽

2014 ◽

Vol 9 (11) ◽

pp. 1030-1036 ◽

Cited By ~ 5

Author(s):

Yaqiu Lin ◽

Yanying Zhao ◽

Ruiwen Li ◽

Jiaqi Gong ◽

Yucai Zheng ◽

...

Keyword(s):

Mrna Level ◽

Biological Significance ◽

C2c12 Cells ◽

Myoblast Differentiation ◽

C2c12 Myoblast ◽

Mrna Levels ◽

Transfected Cells ◽

Myosin Heavy Chain Isoform ◽

Important Mediator

AbstractPGC-1α has been implicated as an important mediator of functional capacity of skeletal muscle. However, the role of PGC-1α in myoblast differentiation remains unexplored. In the present study, we observed a significant up-regulation of PGC-1α expression during the differentiation of murine C2C12 myoblast. To understand the biological significance of PGC-1α up-regulation in myoblast differentiation, C2C12 cells were transfected with murine PGC-1α cDNA and siRNA targeting PGC-1α, respectively. PGC-1α over-expressing clones fused to form typical myotubes with higher mRNA level of myosin heavy chain isoform I (MyHCI) and lower MyHCIIX. No obvious differentiation was observed in PGC-1α-targeted siRNA-transfected cells with marked decrement of mRNA levels of MyHCI and MyHCIIX. Furthermore, PGC-1α increased the expression of MyoD and MyoG in C2C12 cells, which controlled the commitment of precursor cells to myotubes. These results indicate that PGC-1α is associated with myoblast differentiation and elevates MyoD and MyoG expression levels in C2C12 cells.

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Cytolethal Distending Toxin Is Essential for Helicobacter hepaticus Colonization in Outbred Swiss Webster Mice

Infection and Immunity ◽

10.1128/iai.73.6.3559-3567.2005 ◽

2005 ◽

Vol 73 (6) ◽

pp. 3559-3567 ◽

Cited By ~ 68

Author(s):

Zhongming Ge ◽

Yan Feng ◽

Mark T. Whary ◽

Prashant R. Nambiar ◽

Shilu Xu ◽

...

Keyword(s):

Mrna Level ◽

Interleukin 10 ◽

Mouse Strains ◽

Cytolethal Distending Toxin ◽

Mrna Levels ◽

Helicobacter Hepaticus ◽

Male Mice ◽

Susceptible Mouse ◽

Female Mice ◽

Ifn Γ

ABSTRACT Helicobacter hepaticus, which induces chronic hepatitis and typhlocolitis in susceptible mouse strains, produces a cytolethal distending toxin (CDT) consisting of CdtA, CdtB, and CdtC. A cdtB-deficient H. hepaticus isogenic mutant (HhcdtBm7) was generated and characterized for colonization parameters in four intestinal regions (jejunum, ileum, cecum, and colon) of outbred Swiss Webster (SW) mice. Inactivation of the cdtB gene abolished the ability of HhcdtBm7 to colonize female mice at both 8 and 16 weeks postinfection (wpi), whereas HhcdtBm7 colonized all of four intestinal regions of three of five males at 8 wpi and then was eliminated by 16 wpi. Wild-type (WT) H. hepaticus was detected in the corresponding intestinal regions of both male and female mice at 8 and 16 wpi; however, colonization levels of WT H. hepaticus in the cecum and colon of male mice were approximately 1,000-fold higher than in females (P < 0.0079) at 16 wpi. Infection with WT H. hepaticus, but not HhcdtBm7, at 8 wpi was associated with significantly increased mRNA level of ileal and cecal gamma interferon (IFN-γ) in females (P < 0.016 and 0.031 between WT H. hepaticus-infected and sham-dosed females, respectively). In contrast, the mRNA levels of IFN-γ were significantly higher in the colon (P < 0.0079) and trended to be higher in the cecum (P < 0.15) in the HhcdtBm7-colonized male mice versus the sham-dosed controls at 8 wpi. In addition, mRNA levels of ileal IFN-γ were significantly higher in the control females than males at 8 wpi (P < 0.016). There were significantly higher Th1-associated immunoglobulin G2a (IgG2a), Th2-associated IgG1 and mucosal IgA (P < 0.002, 0.002, 0.002, respectively) responses in the mice infected with WT H. hepaticus when compared to HhcdtBm7 at 16 wpi. Colonic interleukin-10 (IL-10) expressions at 16 wpi were significantly lower in both female and male mice colonized by WT H. hepaticus or in males transiently colonized through 8 wpi by HhcdtBm7 versus control mice (P < 0.0159). These lines of evidence indicate that (i) H. hepaticus CDT plays a crucial role in the persistent colonization of H. hepaticus in SW mice; (ii) SW female mice are more resistant to H. hepaticus colonization than male mice; (iii) there was persistent colonization of WT H. hepaticus in cecum, colon, and jejunum but only transient colonization of H. hepaticus in the ileum of female mice; (iv) H. hepaticus colonization was associated with down-regulation of colonic IL-10 production.

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Abstract 544: Strenuous Exercise and Quercetin Intake Differentially Modulate PCSK9 and ANGPLT4 in Normal C57BL6 Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.544 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Halleh Mahini ◽

Dhuha Alsayrafi ◽

Tong Wu ◽

Mahdi Garelnabi

Keyword(s):

Lipid Metabolism ◽

Normal Mouse ◽

Mrna Level ◽

Exercise Group ◽

Strenuous Exercise ◽

Mrna Levels ◽

Moderate Exercise ◽

Pcsk9 Gene ◽

Lipids Metabolism

Introduction: We previously reported that intake of quercetin during moderate exercise modulate lipid metabolism in LDLr -/- C57BL6 mice. The current study investigates the role of strenuous exercise and quercetin on lipids metabolism. Study Design: 40 mice were divided into four groups (10 each). These groups are as follows: Control mice, left untreated; control quercetin group, orally supplied with 100 μg/day of quercetin without exercising; exercise group without quercetin, and exercise group with quercetin supplements. The exercise groups were run on a treadmill for 30 minutes, 20-30m/m/ 5 days/week for two month. All animals were on normal mouse chow, at the end of the two month treatment, tissues were collected and expressions of genes associated lipid metabolism were analyzed and the proteins Western Blotting were determined. Results: PCSK9 mRNA level was significantly up-regulated as the result of combination of exercise and quercetin intake (p< 0.05) or quercetin alone. ANGPLT3 mRNA level did not show any significant changes as a result of exercise or quercetin. However, ANGPLT4 mRNA levels significantly down-regulated with the combination after 8 weeks of exercise and quercetin intake compared to both control and Exercise (p < 0.05). ANGPLT4 also decreased with quercetin intake; however this change is not significant. There was a slight change in ANGPLT 4 levels in the exercise group. Conclusion: The combination of strenuous exercise and quercetin intake did not show any positive affect on LDL (plasma LDL levels were measured; however not presented above), this was also reflected by the upregulation of the PCSK9 gene expression. Lipoprotein related genes differentially modulated with the strenuous exercise and quercetin intake. This data suggest that the combination of strenuous exercise and quercetin intake unfavorably impact LDL associated PCSK9 gene; however differentially affect ANGPLT4 levels with the exercise or the combination.

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The role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in Hirschsprung associated enterocolitis

10.21203/rs.3.rs-17106/v1 ◽

2020 ◽

Author(s):

Feng Chen ◽

Xiaoyu Wei ◽

Xiaohua Chen ◽

Lei Xiang ◽

Xinyao Meng ◽

...

Keyword(s):

Western Blotting ◽

Mrna Level ◽

Underlying Mechanism ◽

Mrna Levels ◽

Wild Type ◽

Inflammatory Pathway ◽

Anti Inflammatory ◽

Phosphorylated Stat3 ◽

Morphology Changes

Abstract Background To investigate the role and the underlying mechanism of the α7nAChR-mediated cholinergic anti-inflammatory pathway in the pathogenesis of Hirschsprung(HSCR) associated enterocolitis（HAEC）. Methods Experimental group:twenty-one-day-old Ednrb-/- mice were selected (n=10), with comparable-age wild type(Ednrb+/+) mice controls (n=10). Intestinal samples were collected. The experimental colons were divided into narrow and dilated segments according to morphology changes. The control colons were divided into distal and proximal segments.Colon HE staining was used to judge HAEC.Acetylcholine levels in colon was measured using enzyme-linked immunosorbent assays. Detected phosphorylated Jak2 (p-Jak2), Jak2, phosphorylated Stat3 (p-Stat3), Stat3, phosphorylated IκBα (p-IκBα) and IκBα were studied by Western blotting; mRNA levels of Jak2, Stat3, and IκBα were detected by RT-qPCR. Results Colon HE staining indicated that HAEC mainly occured in the dilated segments of HSCR mice (Ednrb-/- mice) (EDNRB-P).Acetylcholine content in EDNRB-P was significantly lower than that in the narrow segments (EDNRB-D) (P<0.05). Western blotting showed that the Jak2, p-Jak2, Stat3 and p-Stat3 levels in EDNRB-D were significantly higher than those in EDNRB-P (P<0.05). The p-IκBα and IκBα levels in EDNRB-P were significantly higher than those in EDNRB-D(P<0.05). The mRNA levels of Jak2 and Stat3 in EDNRB-D were higher than those in EDNRB-P, but the IκBα mRNA level was significantly lower than that in EDNRB-P (P<0.05). Conclusions During HAEC, the inflammation in the dilated segment was more severe ,while in the narrow segment there was no obvious inflammatory reaction and the content of acetylcholine was higher, which was associated with the α7nAChR-mediated cholinergic anti-inflammatory pathway.

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Effect of GABA-T on Reproductive Function in Female Rats

Animals ◽

10.3390/ani10040567 ◽

2020 ◽

Vol 10 (4) ◽

pp. 567

Author(s):

Wenyu Si ◽

Hailing Li ◽

Tiezhu Kang ◽

Jing Ye ◽

Zhiqiu Yao ◽

...

Keyword(s):

Mrna Level ◽

Reproductive Function ◽

Female Rats ◽

Enzyme Linked Immunosorbent Assay ◽

Mrna Levels ◽

Lactation Performance ◽

Irreversible Inhibitor ◽

Adult Rats ◽

Expression Of Genes

This study explored the role of γ-aminobutyric acid transaminase (GABA-T) in the puberty and reproductive performance of female rats. Immunofluorescence technique, quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution of GABA-T and the expression of genes and hormones in female rats, respectively. The results showed that GABA-T was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and periventricular nucleus (PeN) of the hypothalamus, and in the adenohypophysis, ovarian granulosa cells and oocytes. Abat mRNA level at 28 d was lowest in the hypothalamus and the pituitary; at puberty, it was lowest in the ovary. Abat mRNA level was highest in adults in the hypothalamus; at infancy and puberty, it was highest in the pituitary; and at 21 d it was highest in the ovary. After vigabatrin (GABA-T irreversible inhibitor) was added to hypothalamus cells, the levels of Abat mRNA and Rfrp-3 mRNA were significantly reduced, but Gnrh mRNA increased at the dose of 25 and 50 μg/mL; Kiss1 mRNA was significantly increased but Gabbr1 mRNA was reduced at the 50 μg/mL dose. In prepubertal rats injected with vigabatrin, puberty onset was delayed. Abat mRNA, Kiss1 mRNA and Gnrh mRNA levels were significantly reduced, but Rfrp-3 mRNA level increased in the hypothalamus. Vigabatrin reduced the concentrations of GABA-T, luteinizing hormone (LH) and progesterone (P4), and the ovarian index. Lactation performance was reduced in adult rats with vigabatrin treatment. Four hours after vigabatrin injection, the concentrations of GABA-T and LH were significantly reduced in adult and 25 d rats, but follicle-stimulating hormone (FSH) increased in 25 d rats. In conclusion, GABA-T affects the reproductive function of female rats by regulating the levels of Gnrh, Kiss1 and Rfrp-3 in the hypothalamus as well as the concentrations of LH and P4.

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Role of α2-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00746.2001 ◽

2002 ◽

Vol 283 (1) ◽

pp. R218-R226 ◽

Cited By ~ 24

Author(s):

Alexander V. Gourine ◽

Valery N. Gourine ◽

Yohannes Tesfaigzi ◽

Nathalie Caluwaerts ◽

Fred Van Leuven ◽

...

Keyword(s):

Mrna Level ◽

Physiological Role ◽

Mrna Levels ◽

Wild Type ◽

Cytokine Responses ◽

Α2 Macroglobulin ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

α2-Macroglobulin (α2M) is not only a proteinase inhibitor in mammals, but it is also a specific cytokine carrier that binds pro- and anti-inflammatory cytokines implicated in fever, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). To define the role of α2M in regulation of febrile and cytokine responses, wild-type mice and mice deficient in α2M (α2M −/−) were injected with lipopolysaccharide (LPS). Changes in body temperature as well as plasma levels of IL-1β, IL-6, and TNF-α and hepatic TNF-α mRNA level during fever in α2M −/− mice were compared with those in wild-type control mice. The α2M −/− mice developed a short-term markedly attenuated (ANOVA, P < 0.05) fever in response to LPS (2.5 mg/kg ip) compared with the wild-type mice. At 1.5 h after injection of LPS, the plasma concentration of TNF-α, but not IL-1β or IL-6, was significantly lower (by 58%) in the α2M −/− mice compared with their wild-type controls (ANOVA, P < 0.05). There was no difference in hepatic TNF-α mRNA levels between α2M −/− and wild-type mice 1.5 h after injection of LPS. These data support the hypotheses that 1) α2M is important for the normal development of LPS-induced fever and 2) a putative mechanism of α2M involvement in fever is through the inhibition of TNF-α clearance. These findings indicate a novel physiological role for α2M.

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Lysyl oxidase-like 2 is increased in asthma and contributes to asthmatic airway remodelling

European Respiratory Journal ◽

10.1183/13993003.04361-2020 ◽

2022 ◽

pp. 2004361

Author(s):

Jopeth Ramis ◽

Robert Middlewick ◽

Francesco Pappalardo ◽

Jennifer T. Cairns ◽

Iain D. Stewart ◽

...

Keyword(s):

Extracellular Matrix ◽

Lysyl Oxidase ◽

Airway Smooth Muscle Cells ◽

Airway Remodelling ◽

Collagen Deposition ◽

Tissue Remodelling ◽

Asthmatic Airway ◽

Bronchial Biopsies

Airway smooth muscle cells (ASM) are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyper-responsiveness, and airway remodelling. Extracellular matrix (ECM) can influence tissue remodelling pathways, however, to date no study has investigated the effect of ASM ECM stiffness and crosslinking on the development of asthmatic airway remodelling. We hypothesised that TGFβ activation by ASM is influenced by ECM in asthma and sought to investigate the mechanisms involved. This study combines in vitro and in vivo approaches: human ASM cells were used in vitro to investigate basal TGFβ activation and expression of ECM crosslinking enzymes. Human bronchial biopsies from asthmatic and non-asthmatic donors were used to confirm LOXL2 expression ASM. A chronic ovalbumin model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling. We found that ASM cells from asthmatics activated more TGFβ basally than non-asthmatic controls and that diseased cell-derived ECM influences levels of TGFβ activated. Our data demonstrate that the ECM crosslinking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGFβ activation in vitro, and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an ovalbumin mouse model of asthma. These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma.

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Role of interleukin-33 in the clinical pathogenesis of chronic apical periodontitis

Journal of International Medical Research ◽

10.1177/0300060519854630 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3332-3343

Author(s):

Tana Gegen ◽

Yanxia Zhu ◽

Qinnuan Sun ◽

Benxiang Hou

Keyword(s):

Inflammatory Cell ◽

Mrna Level ◽

Rank Correlation ◽

Inflammatory Cells ◽

Apical Periodontitis ◽

Mrna Levels ◽

Interleukin 33 ◽

Receptor Activator ◽

Hematoxylin And Eosin

Objective This study investigated interleukin (IL)-33 expression in chronic apical periodontitis (CAP) lesions and possible relationships with receptor activator of nuclear factor κ-Β ligand (RANKL) and osteoprotegerin (OPG). Methods Inflammatory cell infiltration in CAP lesions and samples of healthy periapical tissue (n = 30 each) was evaluated by hematoxylin and eosin staining. IL-33, RANKL, and OPG expression levels were assessed by immunohistochemistry and real-time PCR. In CAP lesions alone, relationships between mRNA level of IL-33 and mRNA levels of both RANKL and OPG were analyzed by Spearman rank correlation. Results Histological analysis revealed a large number of inflammatory cells in CAP lesions, and immunohistochemistry revealed IL-33-positive cells. There were more IL-33- and RANKL-positive cells in CAP lesions than in healthy periapical tissue, whereas there were fewer OPG-positive cells in CAP lesions than in healthy periapical tissue. In CAP lesions alone, IL-33 mRNA level was negatively correlated with mRNA level of RANKL and positively correlated with mRNA level of OPG. Conclusions IL-33 is highly expressed in CAP lesions, where it is negatively correlated with RANKL and positively correlated with OPG expression. IL-33 may protect against bone resorption via RANKL suppression and OPG induction, and constitutes a potential target for CAP treatment.

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Abstract 3689: Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

Circulation ◽

10.1161/circ.118.suppl_18.s_467-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Koichi Shimizu ◽

Peter Libby ◽

Viviane Z Rocha ◽

Eduardo J Folco ◽

Rica Shubiki ◽

...

Keyword(s):

Lymph Nodes ◽

Antigen Presentation ◽

Allograft Rejection ◽

Cardiac Transplantation ◽

Cardiac Allograft ◽

Mrna Levels ◽

Acute Allograft Rejection ◽

Cardiac Allograft Rejection ◽

Ifn Γ

Background: The S100 calcium-binding proteins MRP-8 (S100A8) and MRP-14 (S100A9) heterodimerize to form MRP-8/14 complexes that regulate myeloid cell function, control inflammatory responses, and serve as an early serum marker for monitoring acute allograft rejection. Despite functioning as a putative pro-inflammatory mediator, the pathophysiological role of MRP-8/14 in cardiovascular disease remains unknown. This study used murine cardiac transplantation to investigate the role of MRP-14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14−/−) lacking MRP-8/14 complexes. Results: In major histocompatibility complex class II allomismatched cardiac transplantation (bm12 donor hearts and C57BL/6 recipients), allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14−/ −recipients compared to > 12 weeks (n = 15, p<0.0001) in wild-type (WT) recipients. At 2 week post-transplantation, allografts in MRP14−/ − recipients had significantly higher parenchymal rejection (PR) scores (2.8 ± 0.8, n=8) than WT recipients (0.8 ± 0.8, n=12, p<0.0001). MRP14−/ − recipients had significantly increased allograft accumulation of T cells and macrophages and mRNA levels of IFN-γ and IFN-γ–associated chemokines (IP-10, Mig, and I-TAC) compared to WT recipients. The MRP14−/− recipients also had significantly more lymphocytes in draining lymph nodes than WT recipients (cell number per lymph nodes: 23.7 ± 0.7 x 105 for MRP14−/− vs. 6.0 ± 0.2 x 105 for WT, p < 0.0001). MRP14−/− dendritic cells (DC) stimulated with IFN-γ expressed significantly higher levels of the co-stimulatory molecules CD86 and ICOSL, and mixed leukocyte reaction using allo-EC-primed MRP14−/− DC resulted in significantly higher antigen-presenting function than WT DC. Conclusion: Taken together, these observations indicate that MRP-8/14 complexes participate in acute allograft rejection by modulating dendritic cell antigen presentation and T cell priming. The unexpected finding that deficiency of MRP-8/14 complexes exacerbates acute allograft rejection indicates that MRP-8/14 has distinct roles in modulating immune cell functions, such as migration and antigen presentation. This research has received full or partial funding support from the American Heart Association, AHA National Center.

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myo-Inositol is an osmolyte in rat liver macrophages (Kupffer cells) but not in RAW 264.7 mouse macrophages

Biochemical Journal ◽

10.1042/bj3260289 ◽

1997 ◽

Vol 326 (1) ◽

pp. 289-295 ◽

Cited By ~ 21

Author(s):

Ulrich WARSKULAT ◽

Christian WEIK ◽

Dieter HÄUSSINGER

Keyword(s):

Rat Liver ◽

Kupffer Cells ◽

Mrna Level ◽

Raw 264.7 ◽

Mrna Levels ◽

Mouse Macrophages ◽

Taurine Uptake ◽

Inositol Uptake ◽

Stimulation Of

The role of myo-inositol as an osmolyte was studied in cultured rat liver macrophages (Kupffer cells). Hyperosmotic exposure of Kupffer cells stimulated myo-inositol uptake and led to an increase in the mRNA levels for the sodium/myo-inositol co-transporter (SMIT). Conversely, hypo-osmotic (205 m-osM) exposure diminished myo-inositol uptake when compared with normo-osmotic (305 m-osM) control incubations. The hyperosmolarity-induced SMIT mRNA increase was counteracted by added myo-inositol or betaine. In contrast with Kupffer cells, there was only a slight hyperosmotic stimulation of myo-inositol uptake in RAW 264.7 mouse macrophages, and the myo-inositol transporter (SMIT) mRNA was not detectable. Further, a slight stimulation of taurine uptake and an increase in taurine transporter (TAUT) mRNA level by hyperosmolarity was observed in RAW 264.7 cells, whereas hypo-osmolarity led to a decrease in taurine uptake and TAUT mRNA level. When Kupffer cells were preloaded with myo-inositol, hypo-osmotic exposure led to a rapid efflux of myo-inositol from the cells. Myo-inositol efflux was also stimulated by phagocytosis of latex particles; however, latex was without effect on the hyperosmolarity-induced increase of SMIT mRNA levels. The results suggest a role of myo-inositol as an osmolyte in rat Kupffer cells but not in RAW 264.7 mouse macrophages. The functional relevance of this osmolyte strategy might lie in the maintenance of cell volume homeostasis during phagocytosis in Kupffer cells; however, the interplay with the other osmolytes betaine and taurine remains to be established.

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