scholarly journals The Influence of Bone Marrow-Secreted IL-10 in a Mouse Model of Cerulein-Induced Pancreatic Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Wey-Ran Lin ◽  
Siew-Na Lim ◽  
Tzung-Hai Yen ◽  
Malcolm R. Alison
Keyword(s):  
Bone Marrow ◽  
Mouse Model ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Pancreatic Fibrosis ◽  
Cell Infiltration ◽  
Collagen Deposition ◽  
Wild Type

This study aimed to understand the role of IL-10 secreted from bone marrow (BM) in a mouse model of pancreatic fibrosis. The severity of cerulein-induced inflammation, fibrosis, and the frequency of BM-derived myofibroblasts were evaluated in the pancreas of mice receiving either a wild-type (WT) BM or an IL-10 knockout (KO) BM transplantation. The area of collagen deposition increased significantly in the 3 weeks after cerulein cessation in mice with an IL-10 KO BM transplant (13.7 ± 0.6% and 18.4 ± 1.1%,p< 0.05), but no further increase was seen in WT BM recipients over this time. The percentage of BM-derived myofibroblasts also increased in the pancreas of the IL-10 KO BM recipients after cessation of cerulein (6.7 ± 1.1% and 11.9 ± 1.3%,p< 0.05), while this figure fell in WT BM recipients after cerulein withdrawal. Furthermore, macrophages were more numerous in the IL-10 KO BM recipients than the WT BM recipients after cerulein cessation (23.2 ± 2.3 versus 15.3 ± 1.7 per HPF,p< 0.05). In conclusion, the degree of fibrosis, inflammatory cell infiltration, and the number of BM-derived myofibroblasts were significantly different between IL-10 KO BM and WT BM transplanted mice, highlighting a likely role of IL-10 in pancreatitis.

scholarly journals The CD40-TRAF6 axis is the key regulator of the CD40/CD40L system in neointima formation and arterial remodeling

Blood ◽  
2008 ◽  
Vol 111 (9) ◽  
pp. 4596-4604 ◽  
Author(s):  
Marjo M. P. C. Donners ◽  
Linda Beckers ◽  
Dirk Lievens ◽  
Imke Munnix ◽  
Johan Heemskerk ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Collagenolytic Activity ◽  
Neointima Formation ◽  
Wild Type ◽  
Vessel Volume ◽  
Necrosis Factor

Abstract We investigated the role of CD40 and CD40L in neointima formation and identified the downstream CD40-signaling intermediates (tumor necrosis factor [TNF]–receptor associated factors [TRAF]) involved. Neointima formation was induced in wild-type, CD40−/−, CD40L−/−, and in CD40−/− mice that contained a CD40 transgene with or without mutations at the CD40-TRAF2,3&5, TRAF6, or TRAF2,3,5&6 binding sites. Compared with wild-type mice, CD40−/− mice showed a significant decrease in neointima formation with increased collagen deposition and decreased inflammatory cell infiltration. Neointima formation was also impaired in wild-type mice reconstituted with CD40−/− bone marrow. In vitro, the capacity of CD40−/− leukocytes to adhere to the endothelium was reduced. Ligated carotid arteries of CD40−/− mice showed a smaller total vessel volume and an impaired remodeling capacity, reflected by decreased gelatinolytic/collagenolytic activity. Comparable results were found in mice with defects in CD40-TRAF6 and CD40-TRAF 2/3/5&6 binding, but not in mice with defects in CD40-TRAF2/3&5 binding. Neointima formation and vascular remodeling in CD40-receptor–deficient mice is impaired, due to a decreased inflammatory cell infiltration and matrix-degrading protease activity, with CD40-TRAF6 signaling as the key regulator. This identifies the CD40-TRAF6 axis as a potential therapeutic target in vascular disease.

scholarly journals Topical Application of Sadat-Habdan Mesenchymal Stimulating Peptide (SHMSP) Accelerates Wound Healing in Diabetic Rabbits

2012 ◽  
Vol 2012 ◽  
pp. 1-6
Author(s):  
Abdulmohsen H. Al-Elq ◽  
Mir Sadat-Ali ◽  
Mohamed Elsharawy ◽  
Ibrahim Al-Habdan ◽  
Fatin Othman Al-Aqeel ◽  
...  
Keyword(s):  
Wound Healing ◽  
Blood Vessel ◽  
Topical Application ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Control Group ◽  
Collagen Deposition ◽  
Peptide Group ◽  
Diabetic Rabbits

Objective. Diminished wound healing is a common problem in diabetic patients due to diminished angiogenesis. SHMSP was found to promote angiogenesis. The present study was carried out to examine the effect of this peptide in healing of wounds in diabetic rabbits.Materials and Methods. Twenty male New Zealand rabbits were used in this study. Diabetes mellitus was induced and the rabbits were randomly divided into two equal groups: control group and peptide group. A-full thickness punch biopsy was made to create a wound of about 10 mm on the right ears of all rabbits. Every day, the wound was cleaned with saline in control groups. In the peptide group, 15 mg of SHMSP was applied after cleaning. On day 15th, all animals were sacrificed, and the wounds were excised with a rim of 5 mm of normal surrounding tissue. Histo-pathological assessment of wound healing, inflammatory cell infiltration, blood vessel proliferation, and collagen deposition was performed.Results. There were no deaths among the groups. There was significant increase in wound healing, blood vessel proliferation and collagen deposition, and significant decrease in inflammatory cell infiltration in the peptide group compared to the control group.Conclusion. Topical application of SHMSP improves wound healing in diabetic rabbits.

scholarly journals The Herbal Cocktail GSYJ Attenuated Airway Inflammatory Cell Infiltration in a Chronic Asthmatic Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chung-Jen Chiang ◽  
Shu-Lun Chang ◽  
Li-Jen Lin
Keyword(s):  
Transcription Factors ◽  
Mouse Model ◽  
Inflammatory Cell ◽  
Expression Profiles ◽  
Lavage Fluid ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Chronic Asthma ◽  
Total Ige ◽  
Expression Of Genes

This study explored the potential therapeutic efficacy of GSYJ in attenuating asthma symptom severity and aimed to determine the immunomodulatory mechanism of GSYJ. A mouse model of chronic asthma induced by repeated Dermatophagoides pteronyssinus (Der p) challenge was established. In addition, 30 minutes before Der p challenge, the mice were orally administered GSYJ (1 g/kg). The mice were sacrificed to evaluate inflammatory cell infiltration, collagen deposition in the lung, total IgE in serum, and expression profiles of various cytokines in bronchoalveolar lavage fluid (BALF) and various genes in lung tissue. Furthermore, 30 minutes after the addition of GSYJ to RAW264.7 cell cultures, 100 ng/ml LPS was added to evaluate the effect of the drug on the LPS-induced expression of genes, proteins, and transcription factors. GSYJ may regulate transcription factors (cJUN/IRF3/NF-κB) to decrease the expression of IL-1β, IL-6, RANTES, and iNOS in macrophages and affect the IL-12, IFN-γ, IL-5, and IL-6 levels in the BALF of mice to relieve asthma symptoms, such as inflammatory cell infiltration, hyperresponsiveness, and increased serum total IgE levels. Therefore, GSYJ has the potential to be developed into a drug treatment for chronic asthma.

scholarly journals Muscle paralysis induces bone marrow inflammation and predisposition to formation of giant osteoclasts

2017 ◽  
Vol 313 (5) ◽  
pp. C533-C540 ◽  
Author(s):  
Brandon J. Ausk ◽  
Leah E. Worton ◽  
Kate S. Smigiel ◽  
Ronald Y. Kwon ◽  
Steven D. Bain ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Resorption ◽  
Time Course ◽  
Inflammatory Cell ◽  
Botulinum Toxin A ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Muscle Paralysis ◽  
Inflammatory Microenvironment ◽  
Tibia Bone

Transient muscle paralysis engendered by a single injection of botulinum toxin A (BTxA) rapidly induces profound focal bone resorption within the medullary cavity of adjacent bones. While initially conceived as a model of mechanical disuse, osteoclastic resorption in this model is disproportionately severe compared with the modest gait defect that is created. Preliminary studies of bone marrow following muscle paralysis suggested acute upregulation of inflammatory cytokines, including TNF-α and IL-1. We therefore hypothesized that BTxA-induced muscle paralysis would rapidly alter the inflammatory microenvironment and the osteoclastic potential of bone marrow. We tested this hypothesis by defining the time course of inflammatory cell infiltration, osteoinflammatory cytokine expression, and alteration in osteoclastogenic potential in the tibia bone marrow following transient muscle paralysis of the calf muscles. Our findings identified inflammatory cell infiltration within 24 h of muscle paralysis. By 72 h, osteoclast fusion and pro-osteoclastic inflammatory gene expression were upregulated in tibia bone marrow. These alterations coincided with bone marrow becoming permissive to the formation of osteoclasts of greater size and greater nuclei numbers. Taken together, our data are consistent with the thesis that transient calf muscle paralysis induces acute inflammation within the marrow of the adjacent tibia and that these alterations are temporally consistent with a role in mediating muscle paralysis-induced bone resorption.

scholarly journals Hepatic recruitment of macrophages promotes nonalcoholic steatohepatitis through CCR2

2012 ◽  
Vol 302 (11) ◽  
pp. G1310-G1321 ◽  
Author(s):  
Kouichi Miura ◽  
Ling Yang ◽  
Nico van Rooijen ◽  
Hirohide Ohnishi ◽  
Ekihiro Seki
Keyword(s):  
Bone Marrow ◽  
Kupffer Cells ◽  
Chemokine Receptor ◽  
Nonalcoholic Steatohepatitis ◽  
Inflammatory Cell ◽  
Therapeutic Potential ◽  
Inflammatory Cell Infiltration ◽  
Cell Infiltration ◽  
Potent Inducer ◽  
Hepatic Macrophages

Inflammatory cell infiltration in the liver is a hallmark of nonalcoholic steatohepatitis (NASH). The chemokine-chemokine receptor interaction induces inflammatory cell recruitment. CC-chemokine receptor (CCR)2 is expressed on hepatic macrophages and hepatic stellate cells. This study aims to investigate the therapeutic potential of CCR2 to NASH. Twenty-two weeks on a choline-deficient amino acid-defined (CDAA) diet induced steatosis, inflammatory cell infiltration, and liver fibrosis with increased CCR2 and monocyte chemoattractant protein (MCP)-1 expression in the wild-type livers. The infiltrated macrophages expressed CD68, CCR2, and a marker of bone marrow-derived monocytes, Ly6C. CCR2−/− mice had less steatosis, inflammatory cell infiltration, and fibrosis, and hepatic macrophages expressing CD68 and Ly6C were decreased. Toll-like receptor (TLR)4−/−, TLR9−/−, and MyD88−/− mice had reduced hepatic macrophage infiltration with decreased MCP-1 and CCR2 expression because TLR signaling is a potent inducer of MCP-1. To assess the role of Kupffer cells at the onset of NASH, Kupffer cells were depleted by liposomal clodronate. The Kupffer cell depletion ameliorated steatohepatitis with a decrease in the MCP-1 expression and recruitment of Ly6C-expressing macrophages at the onset of NASH. Finally, to test the therapeutic potential of targeting CCR2, a CCR2 inhibitor was administered to mice on a CDAA diet. The pharmaceutical inhibition of CCR2 prevented infiltration of the Ly6C-positive macrophages, resulting in an inhibition of liver inflammation and fibrosis. We concluded that CCR2 and Kupffer cells contribute to the progression of NASH by recruiting bone marrow-derived monocytes.

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