Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2.
Links Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2. Iosub R, Klug J, Fijak M, Schneider E, Frohlich S, Blumbach K, Wennemuth G, Sommerhoff CP, Steinhoff M, Meinhardt AJ Pathol. 2006 Apr;208(5):686-98. Links Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2. Iosub R, Klug J, Fijak M, Schneider E, Frohlich S, Blumbach K, Wennemuth G, Sommerhoff CP, Steinhoff M, Meinhardt A. Department of Anatomy and Cell Biology, Unit of Reproductive Biology, Justus Liebig University of Giessen, Germany. Mast cells are involved in early events crucial to inflammation and autoimmune disease. Recently, proteinase-activated receptor-2 (PAR(2)), a G-protein coupled receptor important to injury responses, was shown to be activated by mast cell tryptase. To investigate whether mast cells and PAR(2) are involved in the development and/or aggravation of testicular inflammation, we studied acute and chronic inflammatory models in the rat. In normal testes, PAR(2) was detected immunohistochemically in macrophages, in peritubular cells (PTCs) and in spermatid acrosomes. In experimentally induced autoimmune orchitis (EAO), PAR(2) was strongly upregulated in macrophages and peritubular-like cells, forming concentric layers around granulomas. Mast cells increased 10-fold in number, were more widely distributed throughout the interstitial tissue, and were partially degranulated. Isolated PTCs expressed functional PAR(2), responded to PAR(2) activation by phosphorylating extracellular signal-regulated kinases 1/2 (ERK1/2) and activating protein kinase c, and increased intracellular Ca(2+) concentrations as well as monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta(2) (TGFbeta(2)), and cyclooxygenase-2 (COX-2) mRNA expression. Expression of these inflammatory mediators, together with iNOS, also increased significantly in testes 50 days after EAO. In vivo, expression of cytokines and inflammatory mediators was upregulated after injection of recombinant tryptase (MCP-1, TGFbeta(2), and COX-2) and a specific PAR(2) peptide agonist (MCP-1, TGFbeta(2)) in the testis after 5 h. These results suggest that PAR(2) activation elicited on PTCs by mast cell tryptase contributes to acute testicular inflammation and that this pathogenetic mechanism may also play a role in autoimmune orchitis. PMID: 16450334 [PubMed - indexed for MEDLINE] Related Links Protease-activated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells. [J Pharmacol Exp Ther. 2005] PMID: 15367578 Trypsin stimulates the phosphorylation of p42,44 mitogen-activated protein kinases via the proteinase-activated receptor-2 and protein kinase C epsilon in human cultured prostate stromal cells. [Prostate. 2005] PMID: 15678497 Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins. [J Biol Chem. 2005] PMID: 16027150 Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune orchitis. [J Reprod Immunol. 2003] PMID: 14638441 Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2. [J Clin Invest. 1997] PMID: 9294103 See all Related Articles... Display Summary Brief Abstract AbstractPlus Citation MEDLINE XML UI List LinkOut ASN.1 Related Articles Cited Articles Cited in Books CancerChrom Links Domain Links 3D Domain Links GEO DataSet Links Gene Links Gene (GeneRIF) Links Genome Links Project Links GENSAT Links GEO Profile Links HomoloGene Links Nucleotide Links Nucleotide (RefSeq) Links OMIA Links OMIM (calculated) Links OMIM (cited) Links BioAssay Links Compound Links Compound via MeSH Substance Links Substance via MeSH PMC Links Cited in PMC PopSet Links Probe Links Protein Links Protein (RefSeq) Links SNP Links Structure Links Taxonomy via GenBank UniGene Links UniSTS Links Show 5 10 20 50 100 200 500 Sort by Pub Date First Author Last Author Journal Send to Text File Printer Clipboard E-mail Order .
Department of Anatomy and Cell Biology, Unit of Reproductive Biology, Justus Liebig University of Giessen, Germany.
Mast cells are involved in early events crucial to inflammation and autoimmune disease. Recently, proteinase-activated receptor-2 (PAR(2)), a G-protein coupled receptor important to injury responses, was shown to be activated by mast cell tryptase. To investigate whether mast cells and PAR(2) are involved in the development and/or aggravation of testicular inflammation, we studied acute and chronic inflammatory models in the rat. In normal testes, PAR(2) was detected immunohistochemically in macrophages, in peritubular cells (PTCs) and in spermatid acrosomes. In experimentally induced autoimmune orchitis (EAO), PAR(2) was strongly upregulated in macrophages and peritubular-like cells, forming concentric layers around granulomas. Mast cells increased 10-fold in number, were more widely distributed throughout the interstitial tissue, and were partially degranulated. Isolated PTCs expressed functional PAR(2), responded to PAR(2) activation by phosphorylating extracellular signal-regulated kinases 1/2 (ERK1/2) and activating protein kinase c, and increased intracellular Ca(2+) concentrations as well as monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta(2) (TGFbeta(2)), and cyclooxygenase-2 (COX-2) mRNA expression. Expression of these inflammatory mediators, together with iNOS, also increased significantly in testes 50 days after EAO. In vivo, expression of cytokines and inflammatory mediators was upregulated after injection of recombinant tryptase (MCP-1, TGFbeta(2), and COX-2) and a specific PAR(2) peptide agonist (MCP-1, TGFbeta(2)) in the testis after 5 h. These results suggest that PAR(2) activation elicited on PTCs by mast cell tryptase contributes to acute testicular inflammation and that this pathogenetic mechanism may also play a role in autoimmune orchitis.
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