scholarly journals Cytokine regulation of inflammatory processes in respiratory organs of rats exposed to the combined inhalation of chemicals in low concentrations

2021 ◽  
Vol 100 (3) ◽  
pp. 290-294
Author(s):  
Maria Yu. Barantseva ◽  
Lana N. Mukhamedieva ◽  
Olga A. Dadasheva ◽  
Dmitry S. Ozerov ◽  
Anna A. Pakhomova ◽  
...  

Introduction. Morphological studies of animals (trachea, bronchi, lungs) exposed to the combined inhalation of chemicals in low concentrations showed the progression of structural changes, indicating the activation of inflammation and fibrosis in the lungs. The role of cytokine markers in developing inflammatory and fibrotic processes and remodeling lung tissue has been studied. Materials and methods. Male rats (180-200 g) were exposed to a mixture of chemicals (acetone, acetaldehyde, benzene) in low concentrations of 0.7-1.5; 0.9-1.4; 0.2-0.4 (mg/m3), respectively. The concentrations of IL-6, IL-10, IL-1b, IL-4, TGFβ1, TNFα cytokines (pg/ml) have been measured in the lung homogenate by enzyme-linked immunosorbent assay (ELISA). Microscopic anatomy of the lungs, tracheal wall, bronchi has been studied on the 30th day of exposure and the 15th and 90th days of the recovery period. Results. An increase in interleukin-4 and transforming growth factor TGFβ1 in the homogenate of the lung tissue was shown. An increase in lymphatic follicles, the number of lymphocytes, neutrophils, macrophages, and focal accumulations of eosinophils has been observed in the tracheal wall. In lymphoid infiltrates of the lung tissue - eosinophils, macrophages, and plasmocytes. Accumulation of eosinophilic exudate has been observed in some alveoli. The 90th day of the recovery period is characterized by a significant increase of TGFβ1 in the lung tissue, indicating fibrosis, as evidenced by the rise in the number of fibroblasts between the alveoli in the atelectasis zones of lungs. Conclusion. The chronic combined exposure to the mixture of chemicals in low concentrations is accompanied by a pro-inflammatory process in the lungs with the type II hypersensitivity and increasing IL-4 and TGFβ1 (a key mediator of profibrotic activity).

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 949-957 ◽  
Author(s):  
I Dybedal ◽  
SE Jacobsen

Abstract Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF- beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4- , and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF- beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF- beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors.


2007 ◽  
Vol 21 (4) ◽  
pp. 389-394 ◽  
Author(s):  
Huabin Li ◽  
Hongyan Jiang ◽  
Lei Cheng ◽  
Yun Oh ◽  
Geng Xu

Background Chronic rhinosinusitis (CRS) may cover different disease entities, and the pathogenic mechanism remains unclear. Methods The aim of this study was to evaluate the expression of chloride channel protein CLC-2 and CLC-3 in CRS without nasal polyps (CRSsNP) and evaluate the roles of interleukin (IL)-4 and transforming growth factor (TGF) beta in the up-regulation of CLC-2 and CLC-3. We detected expression of CLC-2 and CLC-3 in 17 patients with CRSsNP by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and we examined the concentration of TGF-beta, IL-4, IL-5, and interferon (IFN) γ in ethmoid sinus mucosa by enzyme-linked immunosorbent assay (ELISA). Results We found that CLC-2 and CLC-3 is up-regulated in CRSnNP and located in submucosal glands and epithelium of the ethmoid sinus. CLC-2 and CLC-3 mRNA correlated with IL-4 in CRSsNP (r = 0.57 and 0.65; p < 0.05). CLC-2 and CLC-3 mRNA correlated negatively with mucosal TGF-beta in CRSsNP (r = -0.49 and -0.54; p < 0.05). Conclusion We concluded that CLC-2 and CLC-3 is up-regulated in ethmoid mucosa and may affect the development of CRSsNP. TGF-beta and IL-4 may modulate the expression of CLC-2 and CLC-3 in CRSsNP.


2020 ◽  
Vol 11 ◽  
Author(s):  
Maria Elisa Duarte França ◽  
Larissa Sinhorim ◽  
Daniel Fernandes Martins ◽  
Robert Schleip ◽  
Nicolas A. M. M. Machado-Pereira ◽  
...  

Fascia can become rigid and assume a fibrotic pattern due to inflammatory processes. Manipulation of the fascial system (MFS), manual technique targeting connective tissues, is commonly used in clinical practice in pain management. We aimed to verify MFS effects on the connective tissue inflammatory changes in mice. Swiss Mus musculus male mice (n = 44) were distributed into groups: carrageenan without treatment (Car, n = 11), carrageenan with MFS (Car + MFS, n = 12), saline without treatment (n = 10), and saline with MFS (saline + MFS, n = 11). Interleukin 4 (IL-4), IL-6, tumor necrosis factor (TNF), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein 1 (MCP-1) levels were verified by enzyme-linked immunosorbent assay. Neutrophil (Ly-6G), macrophage (F4/80), and nitric oxide synthase 2 (NOS-2) were identified using Western blot. The MFS protocol was applied from the first to the third day after inflammation of the connective tissue of the thoracolumbar region. There was a significant MFS effect on IL-4 (p = 0.02) and TGF-β1 (p = 0.04), without increasing MCP-1, TNF, and IL-6 levels (p &gt; 0.05) on thoracolumbar region from Car + MFS, in comparison with saline. Ly-6G in Car + MFS presented lower levels when compared with saline (p = 0.003) or saline + MFS (0.003). NOS-2 levels were lower in Car + MFS than in saline + MFS (p = 0.0195) or saline (p = 0.003). MFS may have an anti-inflammatory effect, based on TGF-β1 and IL-4. IL-4 may have inhibited neutrophil migration. Lower levels of NOS-2 may be linked to the lack of macrophages, which are responsible for NOS-2 expression.


2016 ◽  
Vol 36 (8) ◽  
pp. 802-812 ◽  
Author(s):  
XH Chang ◽  
A Zhu ◽  
FF Liu ◽  
LY Zou ◽  
L Su ◽  
...  

Nano nickel oxide (NiO), widely used in industry, has recently been discovered to have pulmonary toxicity. However, no subchronic exposure studies about nano NiO-induced pulmonary fibrosis have been reported. The objective of this study was to investigate pulmonary fibrosis induced by nano NiO and its potential mechanism in rats. Male Wistar rats ( n = 40, 200–240 g) were randomized into control group, nano NiO groups (0.015, 0.06, and 0.24 mg/kg), and micro NiO group (0.024 mg/kg). All rats were killed to collect lung tissue after intratracheal instillation of NiO particles twice a week for 6 weeks. To identify pulmonary fibrosis, Masson trichrome staining, hydroxyproline content, and collagen protein expression were performed. The results showed widespread lung fibrotic injury in histological examination and increased content of hydroxyproline, collagen types I and III in rat lung tissue exposed to nano NiO. To explore the potential pulmonary fibrosis mechanism, transforming growth factor beta 1 (TGF- β1) content was measured by enzyme-linked immunosorbent assay, and the messenger RNA expression of key indicators was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The TGF- β1 content was increased in nano NiO exposure groups, as well as the upregulated gene expression of TGF- β1, Smad2, Smad4, matrix metalloproteinase, and tissue inhibitor of metalloproteinase. The findings indicated that nano NiO could induce pulmonary fibrosis, which may be related to TGF- β1 activation.


Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 949-957 ◽  
Author(s):  
I Dybedal ◽  
SE Jacobsen

Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF- beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4- , and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF- beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF- beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors.


Author(s):  
K. Kovacs ◽  
E. Horvath ◽  
J. M. Bilbao ◽  
F. A. Laszlo ◽  
I. Domokos

Electrolytic lesions of the pituitary stalk in rats interrupt adenohypophysial blood flow and result in massive infarction of the anterior lobe. In order to obtain a deeper insight into the morphogenesis of tissue injury and to reveal the sequence of events, a fine structural investigation was undertaken on adenohypophyses of rats at various intervals following destruction of the pituitary stalk.The pituitary stalk was destroyed electrolytically, with a Horsley-Clarke apparatus on 27 male rats of the R-Amsterdam strain, weighing 180-200 g. Thirty minutes, 1,2,4,6 and 24 hours after surgery the animals were perfused with a glutaraldehyde-formalin solution. The skulls were then opened and the pituitary glands removed. The anterior lobes were fixed in glutaraldehyde-formalin solution, postfixed in osmium tetroxide and embedded in Durcupan. Ultrathin sections were stained with uranyl acetate and lead citrate and investigated with a Philips 300 electron microscope.


Author(s):  
Sritharadol Rutthapol ◽  
Chunhachaichana Charisopon ◽  
Kumlungmak Sukanjana ◽  
Buatong Wilaiporn ◽  
Dechraksa Janwit ◽  
...  

ABSTRACT This study evaluated the effect of mupirocin topical spray on burn wound healing in a rat model. Fifteen male Sprague Dawley rats were used to create full-thickness burns on the rat dorsum using a cylindrical stainless steel rod. The rats were topically treated with normal saline solution (NSS), mupirocin spray, ointment, and solution. The wound size and morphological evaluation were investigated by photographs and clinical criterions for wound healing. The histology was observed by hematoxylin and eosin (HandE) staining assay. The immunohistochemical study was evaluated by detection of transforming growth factor-beta 1 (TGF-β1), and the ratio of matrix metalloproteinase-9 to the tissue inhibitor of matrix metalloproteinase-1 (MMP-9/TIMP-1) was quantified using the enzyme-linked immunosorbent assay (ELISA) assay. A complete healing was observed at 28 days in all treatments. Mupirocin formulations accelerated the wound healing faster than NSS in size. However, the clinical criteria indicated a desirable skin appearance in the mupirocin spray and ointment treated groups. The histological evaluations showed no differences between the treatments while the immunohistochemical study revealed that all treatments reduced the level of TGF-β1 over time, particularly on day 28 in the mupirocin spray and ointment treated groups. The MMP-9/TIMP-1 ratio was significantly lower in the mupirocin spray and ointment treated groups than in the NSS and mupirocin solution groups. This study shows the safety and efficacy in the use of mupirocin topical spray. The topical mupirocin spray is an alternative suitable for development as a human topical anti-infective and wound protection spray.


Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.


2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Hong-Xing Liao ◽  
Zhi-Hui Zhang ◽  
Hui-Lin Chen ◽  
Ying-Mei Huang ◽  
Zhan-Liang Liu ◽  
...  

Abstract Background Hyaluronan (HA) metabolism by chondrocytes is important for cartilage development and homeostasis. However, information about the function of circular RNAs (circRNAs) in HA metabolism is limited. We therefore profiled the role of the novel HA-related circRNA circHYBID in the progression of osteoarthritis (OA). Methods CircHYBID function in HA metabolism in chondrocytes was investigated using gain-of-function experiments, and circHYBID mechanism was confirmed via bioinformatics analysis and luciferase assays. The expression of circHYBID–hsa-miR-29b-3p–transforming growth factor (TGF)-β1 axis was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. CircHYBID, TGF-β1, and HA levels in cartilage samples were evaluated using qRT-PCR and pathological examination. Enzyme-linked immunosorbent assay was used to assess HA accumulation in chondrocyte supernatant. Results CircHYBID expression was significantly downregulated in damaged cartilage samples compared with that in the corresponding intact cartilage samples. CircHYBID expression was positively correlated with alcian blue score. Interleukin-1β stimulation in chondrocytes downregulated circHYBID expression and decreased HA accumulation. Gain-of-function experiments revealed that circHYBID overexpression in chondrocytes increased HA accumulation by regulating HA synthase 2 and HYBID expression. Further mechanism analysis showed that circHYBID upregulated TGF-β1 expression by sponging hsa-miR-29b-3p. Conclusions Our results describe a novel HA-related circRNA that could promote HA synthesis and accumulation. The circHYBID–hsa-miR-29b-3p–TGF-β1 axis may play a powerful regulatory role in HA metabolism and OA progression. Thus, these findings will provide new perspectives for studies on OA pathogenesis, and circHYBID may serve as a potential target for OA therapy.


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