PMID- 16450334
OWN - NLM
STAT- MEDLINE
DCOM- 20060503
LR  - 20091119
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 208
IP  - 5
DP  - 2006 Apr
TI  - Development of testicular inflammation in the rat involves activation of 
      proteinase-activated receptor-2.
PG  - 686-98
AB  - 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.
FAU - Iosub, R
AU  - Iosub R
AD  - Department of Anatomy and Cell Biology, Unit of Reproductive Biology, Justus 
      Liebig University of Giessen, Germany.
FAU - Klug, J
AU  - Klug J
FAU - Fijak, M
AU  - Fijak M
FAU - Schneider, E
AU  - Schneider E
FAU - Frohlich, S
AU  - Frohlich S
FAU - Blumbach, K
AU  - Blumbach K
FAU - Wennemuth, G
AU  - Wennemuth G
FAU - Sommerhoff, C P
AU  - Sommerhoff CP
FAU - Steinhoff, M
AU  - Steinhoff M
FAU - Meinhardt, A
AU  - Meinhardt A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptor, PAR-2)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Autoimmune Diseases/*metabolism/pathology
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Inflammation Mediators/metabolism
MH  - Macrophages/metabolism
MH  - Male
MH  - Mast Cells/pathology
MH  - Mitogen-Activated Protein Kinase 1/physiology
MH  - Mitogen-Activated Protein Kinase 3/physiology
MH  - Orchitis/*metabolism/pathology
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, PAR-2/*metabolism
MH  - Testis/metabolism
EDAT- 2006/02/02 09:00
MHDA- 2006/05/04 09:00
CRDT- 2006/02/02 09:00
PHST- 2006/02/02 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2006/02/02 09:00 [entrez]
AID - 10.1002/path.1938 [doi]
PST - ppublish
SO  - J Pathol. 2006 Apr;208(5):686-98. doi: 10.1002/path.1938.