Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2

Iosub, Radu; Klug, Jörg; Fijak, Monika; Schneider, Eva; Fröhlich, Suada; Blumbach, Katrin; Wennemuth, Gunther; Sommerhoff, CP; Steinhoff, Martin; Meinhardt, Andreas

doi:10.1002/path.1938

Cited by 41 publications

(35 citation statements)

References 49 publications

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“…In our study we also found that TNF-␣ induced the expression and the secretion of MCP-1 and IL-6, which are considered prototype inflammatory markers and are involved in the attraction of immune cells to sites of inflammation (48,49). Production of cytokines, in general, and MCP-1 and IL-6 in particular, is in line with reports of rodent peritubular cells, which are known to secrete a number of cytokines (9).…”

Section: Discussionsupporting

confidence: 89%

Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

et al. 2008

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Testicular peritubular cells are myofibroblastic cells, which represent the major cellular components of the wall of the seminiferous tubules. In men their phenotypic characteristics, including possible secretory activity and regulation, are not well known, in neither normal nor pathologically altered testes. Especially in testes of men with impaired spermatogenesis, the cytoarchitecture of the tubular wall is frequently remodeled and presents fibrotic thickening, increased innervation, and infiltration by macrophages and mast cells. The latter are two sources of TNF-alpha. The purpose of our study was to explore human testicular peritubular cells and mechanisms of their regulation. To this end we primarily studied cultured human testicular peritubular cells (HTPCs), isolated from adult human testes. Having established that HTPCs express TNF-alpha receptors 1 and 2 and respond to recombinant human TNF-alpha by a rapid phosphorylation of ERK1/2, we used complementary approaches, including gene array/RT-PCR studies, Western blotting/immunocytochemistry, and ELISA techniques to study phenotypic characteristics of HTPCs and actions of TNFalpha. We found that HTPCs express the nerve growth factor gene and TNF-alpha-stimulated mRNA levels and secretion of nerve growth factor in a dose- and time-dependent manner. Similarly, monocyte chemoattractant protein-1 was identified as a product of HTPCs, which was regulated by TNF-alpha in a concentration- and time-dependent manner. TNF-alpha furthermore strongly enhanced expression and/or synthesis of other inflammatory molecules, namely IL-6 and cyclooxygenase-2. Active cyclooxygenase-2 is indicated by increased prostaglandin D2 levels. In addition, intercellular adhesion molecule-1, which was not detected at protein level in the absence of TNF-alpha, was induced upon TNF-alpha stimulation. In conclusion, these results provide novel insights into the nature of human peritubular cells, which are able to secrete potent signaling molecules and are regulated by TNF-alpha. These results also hint to an as-yet-unknown role of peritubular cells in normal human testis and involvement in the pathomechanisms associated with impaired spermatogenesis in men.

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Section: Discussionsupporting

confidence: 89%

Exploring Human Testicular Peritubular Cells: Identification of Secretory Products and Regulation by Tumor Necrosis Factor-α

et al. 2008

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“…Mast cells involve in the granuloma formation in the testis through proteinase-activated receptor-2 (PAR2) activation. PAR2 is localized to the MPCs, macrophages, and acrosomes of spermatids in rat testis, and involved in the development of testicular inflammation (Iosub et al, 2006). PAR2 expression in EAO models is upregulated and associated with granuloma formation.…”

Section: Cellular Mechanisms Of Testicular Immune Privilegementioning

confidence: 99%

Structural, cellular and molecular aspects of immune privilege in the testis

Li¹,

Wang²,

Han³

2012

Front. Immun.

178

163

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The testis presents a special immunological environment, considering its property of immune privilege that tolerates allo- and auto-antigens. Testicular immune privilege was once believed to be mainly based on the sequestration of antigens from the immune system by the blood–testis barrier in the seminiferous epithelium. Substantial evidence supports the view that the combination of physical structure, testicular cells, and cytokines controls immune responses in the testis to preserve the structural and functional integrity of testicular immune privilege. Both systemic immune tolerance and local immunosuppression help maintain the immune privilege status. Constitutive expression of anti-inflammatory factors in testicular cells is critical for local immunosuppression. However, the testis locally generates an efficient innate immune system against pathogens. Disruption of these mechanisms may lead to orchitis and impair fertility. This review article highlights the current understanding of structural, cellular, and molecular mechanisms underlying the unique immune environment of the testis, particularly its immune privilege status.

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“…Tryptase activates PAR 2 on keratinocytes [47], endothelial cells [48], testicular peritubular cells [49], and other types of cells (reviewed in [50]). Tryptase is a less potent activator of PAR 2 than trypsin, and the ability of tryptase to activate PAR 2 dramatically decreases depending on receptor glycosylation at a site close to the activation site [40,41].…”

Section: R) Available Receptor Antagonists or Inhibitorsmentioning

confidence: 99%