Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune orchitis

Guazzone, Vanesa Anabella; Rival, Claudia; Denduchis, Berta; Lustig, Livia

doi:10.1016/j.jri.2003.08.001

Cited by 54 publications

(45 citation statements)

References 23 publications

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“…Some authors demonstrated that, in the testicular fluid of rats with orchitis, there was a significant increase in MCP-1, compared with control group (55). In fact, testicular inflammation in vivo causes an influx of new monocytes and macrophages in the testis and chemokines are involved in leukocyte trafficking (6).…”

Section: Discussionmentioning

confidence: 99%

Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation

Riccioli

Starace

Galli

et al. 2006

The Journal of Immunology

112

113

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TLRs play a crucial role in early host defense against invading pathogens. In the seminiferous epithelium, Sertoli cells are the somatic nurse cells that mechanically segregate germ cell autoantigens by means of the blood-tubular barrier and create a microenvironment that protects germ cells from both interstitial and ascending invading pathogens. The objective of this study was to examine TLR expression and their functional responses to specific agonists in mouse Sertoli cells. We measured the expression of TLR2, TLR4, TLR5, and TLR6 mRNAs and confirmed by FACS analysis the presence of proteins TLR2 and TLR5 on which we focused our study. Stimulation of Sertoli cells with macrophage-activating lipopeptide-2, agonist of TLR2/TLR6, and with flagellin, agonist of TLR5, induces augmented secretion of the chemokine MCP-1. To assess the functional significance of MCP-1 production following TLR stimulation, conditioned medium from either macrophage-activating lipopeptide-2 or flagellin-treated Sertoli cells was tested for in vitro chemotaxis assay, and a significant increase of macrophage migration was observed in comparison with unstimulated conditioned medium. Moreover, we studied the role of NF-κB and of MAPKs in regulating TLR-mediated MCP-1 secretion by using inhibitors specific for each transduction pathway and we demonstrated a pivotal role of the IκB/NF-κB and JNK systems. In addition, TLR2/TLR6 and TLR5 stimulation induces increased ICAM-1 expression in Sertoli cells. Collectively, this study demonstrates the novel ability of Sertoli cells to potentially respond to a wide variety of bacteria through TLR stimulation.

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Section: Discussionmentioning

confidence: 99%

Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation

Riccioli

Starace

Galli

et al. 2006

The Journal of Immunology

112

113

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“…In the later stages of the disease, these infiltrates can form granulomas. The final phase of EAO consists of the progressive apoptosis of germ cells, which leads to aspermatogenesis and thus sterility (16)(17)(18)(19)(20). Decreased levels of testosterone and increased FSH concentrations in serum indicate that the detrimental influence of EAO is not limited to testicular germ cells alone but also extends to the dysfunction of the somatic, Sertoli, and Leydig cells (21).…”

mentioning

confidence: 99%

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

Fijak

Schneider

Klug

et al. 2011

The Journal of Immunology

182

154

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Despite the immune-privileged status of the male genital tract, infection and inflammation of the male genital tract are important etiological factors in male infertility. A common observation in clinical and experimental orchitis as well as in systemic infection and inflammation are decreased levels of testosterone. Emerging data point to an immunosuppressive role of testosterone. In our study, we substituted testosterone levels in experimental autoimmune orchitis (EAO) in rat by s.c. testosterone implants. EAO development was reduced to 17% when animals were treated with low-dose testosterone implants (3 cm long, EAO+T3) and to 33% when rats were supplied with high-dose testosterone implants (24 cm, EAO+T24) compared with 80% of animals developing disease in the EAO control group. In the testis, testosterone replacement in EAO animals prevented the accumulation of macrophages and significantly reduced the number of CD4+ T cells with a strong concomitant increase in the number of regulatory T cells (CD4+CD25+Foxp3+) compared with EAO control. In vitro testosterone treatment of naive T cells led to an expansion of the regulatory T cell subset with suppressive activity and ameliorated MCP-1–stimulated chemotaxis of T lymphocytes in a Transwell assay. Moreover, expression of proinflammatory mediators such as MCP-1, TNF-α, and IL-6 in the testis and secretion of Th1 cytokines such as IFN-γ and IL-2 by mononuclear cells isolated from testicular draining lymph nodes were decreased in the EAO+T3 and EAO+T24 groups. Thus, our study shows an immunomodulatory and protective effect of testosterone substitution in the pathogenesis of EAO and suggests androgens as a new factor in the differentiation of regulatory T cells.

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“…We previously described an increase of CCL2 (Guazzone et al 2003) and CCL4 ) in the testis of rats with orchitis. The highest CCL2 concentration was associated with the highest number of mononuclear cells expressing CCL2 receptor (CCR2) detected within the testicular interstitium of EAO rats (Guazzone et al 2003).…”

Section: Introductionmentioning

confidence: 91%

“…The highest CCL2 concentration was associated with the highest number of mononuclear cells expressing CCL2 receptor (CCR2) detected within the testicular interstitium of EAO rats (Guazzone et al 2003). Chemokines affect cells by activating surface receptors that are seven-transmembrane domain G-protein-coupled receptors and leukocyte responses to particular chemokines are determined by their complement of chemokine receptors.…”

Section: Introductionmentioning

confidence: 99%

Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis

Guazzone

Jacobo²,

Denduchis³

et al. 2012

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The testis is considered an immunologically privileged site where germ cell antigens are protected from autoimmune attack. Yet in response to infections, inflammatory diseases, or trauma, there is an influx of leukocytes to testicular interstitium. Interactions between endothelial cells (EC) and circulating leukocytes are implicated in the initiation and evolution of inflammatory processes. Chemokines are a family of chemoattractant cytokines characterized by their ability to both recruit and activate cells. Thus, we investigated the expression of CCL3, its receptors, and adhesion molecules CD31 and CD106 in an in vivo model of experimental autoimmune orchitis (EAO). In EAO, the highest content of CCL3 in testicular fluid coincides with onset of the disease. However, CCL3 released in vitro by testicular macrophages is higher during the immunization period. The specific chemokine receptors, CCR1 and CCR5, were expressed by testicular monocytes/macrophages and an increased number of CCR5C cells was associated with the degree of testicular lesion. EC also play an essential role by facilitating leukocyte recruitment via their ability to express cell surface adhesion molecules that mediate interactions with leukocytes in the bloodstream. Rats with EAO showed a significant increase in the percentage of CD31C EC that upregulate the expression of CD106. The percentage of leukocytes isolated from peripheral blood and lymph nodes expressing CD49d (CD106 ligand) also increases during orchitis. These data suggest that cell adhesion molecules, in conjunction with chemokines, contribute to the formation of a chemotactic gradient within the testis, causing the leukocyte infiltration characteristic of EAO histopathology.

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Monocyte chemoattractant protein-1 (MCP-1/CCL2) in experimental autoimmune orchitis

Cited by 54 publications

References 23 publications

Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation

Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation

Testosterone Replacement Effectively Inhibits the Development of Experimental Autoimmune Orchitis in Rats: Evidence for a Direct Role of Testosterone on Regulatory T Cell Expansion

Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis

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