scholarly journals Effects of Trauma-Hemorrhage and IL-6 Deficiency on Splenic Immune Function in a Murine Trauma Model

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
P. Mommsen ◽  
T. Barkhausen ◽  
C. Zeckey ◽  
H. Andruszkow ◽  
C. Krettek ◽  
...  
Keyword(s):  
Immune Function ◽  
Femoral Fracture ◽  
Cytokine Production ◽  
Early Stage ◽  
Production Capacity ◽  
Femoral Shaft ◽  
Shaft Fracture ◽  
Trauma Model

Splenic immune function is known to be depressed following hemorrhage. The present study investigates the effects of femoral shaft fracture, isolated or in combination with hemorrhage, on early stage cytokine production capacity of splenocytes and observes the role of IL-6 under these conditions. Male IL-6 knockout (IL-6−/−) and wild-type mice (WT) were randomly divided into three groups: sham (S), isolated femoral fracture (Fx), and femoral fracture + volume controlled hemorrhage (TH-Fx) ( per group). Animals were sacrificed four hours after induction of hemorrhage and fracture. Cytokine release (TNF-α, IL-6, and IL-10) of isolated and LPS-stimulated splenocytes was determined by cytometric bead array. Femoral fracture with or without hemorrhage caused a suppression of in vitro cytokine production capacity of splenocytes at an early posttraumatic stage in WT and IL-6−/−. In the absence of IL-6, the profile of splenic cytokine secretion is significantly altered, identifying this cytokine as a potential therapeutic target to modulate the posttraumatic immune response.

scholarly journals The role of Neuropilin-1 in COVID-19

2021 ◽  
Vol 17 (1) ◽  
pp. e1009153
Author(s):  
Bindu S. Mayi ◽  
Jillian A. Leibowitz ◽  
Arden T. Woods ◽  
Katherine A. Ammon ◽  
Alphonse E. Liu ◽  
...  
Keyword(s):  
Immune Function ◽  
Viral Entry ◽  
Axonal Guidance ◽  
Cell Surface Receptor ◽  
Neuropilin 1 ◽  
Surface Receptor ◽  
The Central Nervous System

Neuropilin-1 (NRP-1), a member of a family of signaling proteins, was shown to serve as an entry factor and potentiate SARS Coronavirus 2 (SARS-CoV-2) infectivity in vitro. This cell surface receptor with its disseminated expression is important in angiogenesis, tumor progression, viral entry, axonal guidance, and immune function. NRP-1 is implicated in several aspects of a SARS-CoV-2 infection including possible spread through the olfactory bulb and into the central nervous system and increased NRP-1 RNA expression in lungs of severe Coronavirus Disease 2019 (COVID-19). Up-regulation of NRP-1 protein in diabetic kidney cells hint at its importance in a population at risk of severe COVID-19. Involvement of NRP-1 in immune function is compelling, given the role of an exaggerated immune response in disease severity and deaths due to COVID-19. NRP-1 has been suggested to be an immune checkpoint of T cell memory. It is unknown whether involvement and up-regulation of NRP-1 in COVID-19 may translate into disease outcome and long-term consequences, including possible immune dysfunction. It is prudent to further research NRP-1 and its possibility of serving as a therapeutic target in SARS-CoV-2 infections. We anticipate that widespread expression, abundance in the respiratory and olfactory epithelium, and the functionalities of NRP-1 factor into the multiple systemic effects of COVID-19 and challenges we face in management of disease and potential long-term sequelae.

scholarly journals Effects of Parathyroid Hormone on Immune Function

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Abdallah Sassine Geara ◽  
Mario R. Castellanos ◽  
Claude Bassil ◽  
Georgia Schuller-Levis ◽  
Eunkue Park ◽  
...  
Keyword(s):  
T Cells ◽  
Parathyroid Hormone ◽  
Immune Function ◽  
Clinical Significance ◽  
Uremic Toxins ◽  
Immunomodulatory Effects ◽  
Uremic Patients

Parathyroid hormone (PTH) function as immunologic mediator has become interesting with the recent usage of PTH analogue (teriparatide) in the management of osteoporosis. Since the early 1980s, PTH receptors were found on most immunologic cells (neutrophils, B and T cells). The in vitro evaluations for a possible role of PTH as immunomodulator have shown inconsistent results mainly due to methodological heterogeneity of these studies: it used different PTH formulations (rat, bovine, and human), at different dosages and different incubating periods. In some of these studies, the lymphocytes were collected from uremic patients or animals, which renders the interpretation of the results problematic due to the effect of uremic toxins. Parathyroidectomy has been found to reverse the immunologic defect in patients with high PTH levels. Nonetheless, the clinical significance of these findings is unclear. Further studies are needed to define if PTH does have immunomodulatory effects.

scholarly journals Hedgehog Inhibitors Suppress Osteoclastogenesis in In Vitro Cultures, and Deletion of Smo in Macrophage/Osteoclast Lineage Prevents Age-Related Bone Loss

2020 ◽  
Vol 21 (8) ◽  
pp. 2745
Author(s):  
Yukihiro Kohara ◽  
Ryuma Haraguchi ◽  
Riko Kitazawa ◽  
Yuuki Imai ◽  
Sohei Kitazawa
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Signaling Pathway ◽  
Early Stage ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Age Related ◽  
Hh Signaling

The functional role of the Hedgehog (Hh)-signaling pathway has been widely investigated in bone physiology/development. Previous studies have, however, focused primarily on Hh functions in bone formation, while its roles in bone resorption have not been fully elucidated. Here, we found that cyclopamine (smoothened (Smo) inhibitor), GANT-58 (GLI1 inhibitor), or GANT-61 (GLI1/2 inhibitor) significantly inhibited RANKL-induced osteoclast differentiation of bone marrow-derived macrophages. Although the inhibitory effects were exerted by cyclopamine or GANT-61 treatment during 0–48 h (early stage of osteoclast differentiation) or 48–96 h (late stage of osteoclast differentiation) after RANKL stimulation, GANT-58 suppressed osteoclast formation only during the early stage. These results suggest that the Smo-GLI1/2 axis mediates the whole process of osteoclastogenesis and that GLI1 activation is requisite only during early cellular events of osteoclastogenesis. Additionally, macrophage/osteoclast-specific deletion of Smo in mice was found to attenuate the aging phenotype characterized by trabecular low bone mass, suggesting that blockage of the Hh-signaling pathway in the osteoclast lineage plays a protective role against age-related bone loss. Our findings reveal a specific role of the Hh-signaling pathway in bone resorption and highlight that its inhibitors show potential as therapeutic agents that block osteoclast formation in the treatment of senile osteoporosis.

scholarly journals New insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targets

2017 ◽  
Vol 20 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Elena Sergeevna Kamyshova ◽  
Irina Nikolaevna Bobkova ◽  
Irina Mikhailovna Kutyrina
Keyword(s):  
Diabetic Nephropathy ◽  
Early Detection ◽  
Early Stage ◽  
Biological Fluids ◽  
Renal Tissue ◽  
In Vivo Models ◽  
New Biomarkers

Diabetic nephropathy (DN) is a severe complication of diabetes mellitus associated with the progressive deterioration of renal function. Although microalbuminuria is considered as a gold standard for DN diagnosis, it has limited predictive powers and specificity as a diagnostic tool for the early stage of DN. Therefore, new biomarkers are required for the early detection of DN. Studies using in vitro and in vivo models of DN have revealed an important role of microRNAs (miRNAs), short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression, in DN development. Recent studies have shown that the dysregulation of miRNAs, which is associated with the key features of DN, such as the mesangial expansion and accumulation of extracellular matrix proteins, is related to fibrosis and glomerular dysfunction. Thus, the up- and downregulation of miRNA expression in the renal tissue or biological fluids, including urine, may represent new biomarkers for the diagnosis and monitoring of DN progression. In this review, we highlight the significance of miRNAs as biomarkers for the early detection of DN and emphasise their potential role as a therapeutic target.

scholarly journals Mitogen Kinase Kinase (MKK7) controls cytokine production in vitro and in vivo in mice

2021 ◽  
Author(s):  
Amada D. Caliz ◽  
Hyung-Jin Yoo ◽  
Anastassiia Vertii ◽  
Cathy Tournier ◽  
Roger J. Davis ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Cell Types ◽  
Minor Role ◽  
Cellular Processes ◽  
Mitogen Activated Protein ◽  
And Migration ◽  
Jnk Activation

Mitogen kinase kinase 4 (MKK4) and Mitogen kinase kinase 7 (MKK7) are members of the MAP2K family which can activate downstream mitogen-activated protein kinases (MAPKs). MKK4 has been implicated in the activation of both, c-Jun N-terminal Kinase (JNK) and p38 MAPK, whereas MKK7 only activates JNK in response to different stimuli. The stimuli as well as cell type determine the choice of MAP2K member that mediates the response. In a variety of cell types, the MKK7 contributes to the activation of downstream MAPKs, JNK, which is known to regulate essential cellular processes, such as cell death, differentiation, stress response, and cytokine secretion. Previous studies have implicated the role of MKK7 in stress signaling pathways and cytokine production. However, little is known about the degree to which MKK7 and MKK4 contributes to innate immune response in macrophages as well as during inflammation in vivo. To address this question and elucidate the role of MKK7 and MKK4 in macrophage and in vivo, we developed MKK7- and MKK4-deficient mouse models with tamoxifen-inducible Rosa26 CreERT. This study reports that MKK7 is required for JNK activation both in vitro and in vivo. Additionally, we demonstrated that MKK7 in macrophages is necessary for LPS induced cytokine production and migration which appears to be a major contributor to the inflammatory response in vivo. Whereas MKK4 plays a significant but minor role in cytokine production in vivo.

scholarly journals Interleukin-37b inhibits the growth of murine endometriosis-like lesions by regulating proliferation, invasion, angiogenesis and inflammation

2020 ◽  
Vol 26 (4) ◽  
pp. 240-255
Author(s):  
Yongpei He ◽  
Ting Xiong ◽  
Fang Guo ◽  
Zhenzhen Du ◽  
Yixian Fan ◽  
...  
Keyword(s):  
Early Stage ◽  
Inflammatory Factors ◽  
Epithelial Cell Line ◽  
Vascular Endothelial ◽  
Gynecological Disease ◽  
Endothelial Growth Factor ◽  
In Vitro Treatment

Abstract Endometriosis is a gynecological disease with abnormal expression of interleukin (IL)-37 which can suppress inflammation and the immune system. Here we investigated the role of the IL-37b splice variant in endometriosis in vivo and in vitro. In a murine model of endometriosis, in vivo administration of IL-37b significantly inhibited the development of lesions judged by the number (P = 0.0213), size (P = 0.0130) and weight (P = 0.0152) of lesions. IL-37b had no effect on the early stage of lesion formation, however administration in the growth stage of lesions decreased the number (P = 0.0158), size (P = 0.0158) and weight (P = 0.0258) of lesions compared with PBS control, an effect that was not reversed by macrophage depletion. Expressions of inflammatory factors, matrix metalloproteinases and vascular endothelial growth factor-A mRNA/protein were significantly inhibited in ectopic lesions following IL-37b administration, and in uterine segments treated in vitro. In vitro treatment of uterine segments with IL-37b inhibited phosphorylation of Akt and Erk1/2 in uterine segments. Isolated mouse endometrial stromal treated with IL-37b and transfected with pIL-37b plasmid got suppressed cell proliferation, invasion, angiogenesis and the expression of inflammatory factors. In addition, transfection with pIL-37b significantly decreased the phosphorylation of Akt and Erk1/2. IL-37b also inhibited proliferation and the expression of inflammatory and angiogenesis factors in epithelial cell line RL95–2. These findings suggest that IL-37b may inhibit the growth of lesions by regulating proliferation, invasion, angiogenesis and inflammation through Akt and Erk1/2 signaling pathway.

scholarly journals Study on the Role of Cytc in Response to BmNPV Infection in Silkworm, Bombyx mori (Lepidoptera)

2019 ◽  
Vol 20 (18) ◽  
pp. 4325 ◽  
Author(s):  
Xue-Yang Wang ◽  
Kang-Hui Wu ◽  
Hui-Lin Pang ◽  
Ping-Zhen Xu ◽  
Mu-Wang Li ◽  
...  
Keyword(s):  
Bombyx Mori ◽  
Early Stage ◽  
Malpighian Tubule ◽  
Infection Process ◽  
Insect Vector ◽  
Apoptosis Pathway ◽  
Expression Levels ◽  
Mitochondrial Apoptosis Pathway

Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the primary pathogens of the silkworm. Cytochrome c (cytc) showed a significant response to BmNPV infection in our previous transcriptome study. However, little is known about the role of Bombyx mori cytc (Bmcytc) in resistance to BmNPV infection. In this study, the expression levels analysis of Bmcytc showed stable expression levels in selected tissues of the resistant strain AN following BmNPV infection, while there was downregulation in the susceptible strain p50, except in the malpighian tubule. To further study the role of Bmcytc in viral infection, Bmcytc was knocked down with siRNA in vitro, resulting in significant downregulation of selected downstream genes of the mitochondrial pathway, including Bmapaf, Bmcaspase-Nc, and Bmcaspase-1; this was also confirmed by overexpression of Bmcytc using the pIZT/V5-His-mCherry insect vector, except Bmcaspase-1. Moreover, knockdown of Bmcytc significantly promoted the infection process of BmNPV in vitro, while the infection was inhibited by overexpression of Bmcytc at the early stage and subsequently increased rapidly. Based on these results, we concluded that Bmcytc plays a vital role in BmNPV infection by regulating the mitochondrial apoptosis pathway. Our work provides valuable data for the clarification of the mechanism of silkworm resistance to BmNPV infection.

Transformation by the v-fms oncogene product: role of glycosylational processing and cell surface expression

1985 ◽  
Vol 5 (12) ◽  
pp. 3467-3475
Author(s):  
E J Nichols ◽  
R Manger ◽  
S Hakomori ◽  
A Herscovics ◽  
L R Rohrschneider
Keyword(s):  
Cell Surface ◽  
Gene Product ◽  
Early Stage ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Sarcoma Virus ◽  
Complete Processing ◽  
Oncogene Protein

The effect of glycosylational-processing inhibitors on the synthesis, cell surface expression, endocytosis, and transforming function of the v-fms oncogene protein (gp140fms) was examined in McDonough feline sarcoma virus-transformed Fischer rat embryo (SM-FRE) cells. Swainsonine (SW), a mannosidase II inhibitor, blocked complete processing, but an abnormal v-fms protein containing hybrid carbohydrate structures was expressed on the cell surface. SW-treated SM-FRE cells retained the transformed phenotype. In contrast, two glucosidase I inhibitors (castanospermine [CA] and N-methyl-1-deoxynojirimycin [MdN]) blocked carbohydrate remodeling at an early stage within the endoplasmic reticulum and prevented cell surface expression of v-fms proteins. CA-treated SM-FRE cells reverted to the normal phenotype. Neither SW, CA, nor MdN affected either endocytosis or the tyrosine kinase activity associated with the v-fms gene product in vitro. These results demonstrate the necessity of carbohydrate processing for cell surface expression of the v-fms gene product and illustrate the unique ability to modulate the transformed state of SM-FRE cells with the glycosylational-processing inhibitors CA and MdN.

scholarly journals Enhanced Neutrophil Longevity and Recruitment Contribute to the Severity of Oviduct Pathology during Chlamydia muridarum Infection

2011 ◽  
Vol 79 (10) ◽  
pp. 4029-4041 ◽  
Author(s):  
Lauren C. Frazer ◽  
Catherine M. O'Connell ◽  
Charles W. Andrews ◽  
Matthew A. Zurenski ◽  
Toni Darville
Keyword(s):  
Cytokine Production ◽  
Acute Infection ◽  
Absolute Number ◽  
Neutrophil Apoptosis ◽  
Content Type ◽  
Chlamydia Muridarum ◽  
Reduced Frequency

ABSTRACTOur previous studies revealed that intravaginal infection of mice with a plasmid-deficient strain ofChlamydia muridarum, CM3.1, does not induce the development of oviduct pathology. In this study, we determined that infection with CM3.1 resulted in a significantly reduced frequency and absolute number of neutrophils in the oviducts during acute infection. This reduction in neutrophils was associated with significantly lower levels of neutrophil chemokines in the oviducts and decreased production of neutrophil chemokines by oviduct epithelial cells infected with CM3.1in vitro. Infection with CM3.1 also resulted in an increased frequency of late apoptotic/dead neutrophils in the oviduct. Examination of the ability ofChlamydia trachomatisto prevent neutrophil apoptosisin vitrorevealed thatC. trachomatisstrain D/UW-3/Cx exhibited an enhanced ability to prevent neutrophil apoptosis compared to plasmid-deficient CTD153, and this effect was dependent on the presence of CD14highmonocytes. The presence of monocytes also resulted in enhanced neutrophil cytokine production and increased production of tissue-damaging molecules in response to D/UW-3/Cx relative to results with CTD153. Attempts to use antibody-mediated depletion to discern the specific role of neutrophils in infection control and pathologyin vivorevealed that although Ly6Ghighneutrophils were eliminated from the blood and oviducts with this treatment, immature neutrophils and high levels of tissue-damaging molecules were still detectable in the upper genital tract. These data support the role of neutrophils in chlamydia-induced pathology and reveal that novel methods of depletion must be developed before their role can be specifically determinedin vivo.

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