Experimental Autoimmune Damage to Rat Male Accessory Glands. I. Transfer of Autoimmune Response by Spleen Cells

Depiante-Depaoli, M; Pacheco-Rupil, B; Britos, Sergio A.; Casas, Alejandro

doi:10.1111/j.1600-0897.1984.tb00280.x

Cited by 21 publications

(8 citation statements)

References 15 publications

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“…Further support for the autoimmune nature of CP/CPPS is provided by EAP models in rodents (45)(46)(47). They have been extensively characterized, demonstrating that immunization of rats or mice with prostate gland extracts can induce T cell and Ab responses to prostate Ags, associated with histological evidence of prostate inflammation.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Penna

Amuchastegui

Cossetti

et al. 2006

The Journal of Immunology

116

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On the basis of on the marked inhibitory activity of the vitamin D receptor agonist Elocalcitol on basal and growth factor-induced proliferation of human prostate cells and on its potent anti-inflammatory properties, we have tested its capacity to treat experimental autoimmune prostatitis (EAP) induced by injection of prostate homogenate-CFA in nonobese diabetic (NOD) mice. Administration of Elocalcitol, at normocalcemic doses, for 2 wk in already established EAP significantly inhibits the intraprostatic cell infiltrate, leading to a profound reduction in the number of CD4+ and CD8+ T cells, B cells, macrophages, dendritic cells, and I-Ag7-positive cells. Immunohistological analysis demonstrates reduced cell proliferation and increased apoptosis of resident and infiltrating cells. Significantly decreased production of the proinflammatory cytokines IFN-γ and IL-17 is observed in prostate-draining lymph node T cells from Elocalcitol-treated NOD mice stimulated by TCR ligation. In addition, Elocalcitol treatment reduces IFN-γ production by prostate-infiltrating CD4+ T cells and draining lymph node T cells specific for an immunodominant peptide naturally processed from prostate steroid-binding protein, a prostate-specific autoantigen. Finally, CD4+ splenic T cells from Elocalcitol-treated NOD mice show decreased ability, upon adoptive transfer into NOD.SCID recipients, to induce autoimmune prostatitis, paralleled by a reduced capacity to produce IFN-γ in response to prostate steroid-binding protein. The results indicate that Elocalcitol is able to interfere with key pathogenic events in already established EAP in the NOD mouse. These data show a novel indication for vitamin D receptor agonists and indicate that treatment with Elocalcitol may inhibit the intraprostatic inflammatory response in chronic prostatitis/chronic pelvic pain syndrome patients.

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Section: Discussionmentioning

confidence: 99%

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Penna

Amuchastegui

Cossetti

et al. 2006

The Journal of Immunology

116

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“…Such clones of T cells thus would have escaped deletion in the thymus and would be capable of responding to PSA when presented in an immunogenic form. In addition, immune-mediated prostatitis can be induced in both rats and mice when they are immunized with syngeneic prostate homogenates in the presence of complete Freund's adjuvant, indicating that it is possible to mount a response to endogenous prostate antigens (30)(31)(32). Furthermore, patients with advanced prostate cancer, in which serum PSA levels were greatly increased, also exhibited antibodies to PSA (33).…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific expression of the human prostate-specific antigen gene in transgenic mice: Implications for tolerance and immunotherapy

Chen

Willis

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Human prostate-specific antigen (PSA) has been widely used as a serum marker for cancer of the prostate. The cell type-specific expression of PSA also makes it a potential tumor antigen for prostate cancer immunotherapy. Study of the immunological aspects of PSA within either normal or malignant prostate tissue has been hampered by the lack of a mouse model, because no PSA counterpart has been identified in mice. Using a 14-kb genomic DNA region that encompasses the entire human PSA gene and adjacent f lanking sequences, we generated a series of human PSA transgenic mice. In the six independent lines of transgenic mice generated, the expression of the human PSA transgene, driven by its own cis-acting regulatory elements, is specifically targeted to the prostate. Tissue distribution analysis demonstrated that PSA transgene expression closely follows the human expression pattern. Immunohistochemical analysis of the prostate tissue also showed that the expression of the PSA transgene is confined to the ductal epithelial cells. Despite expressing PSA as a self-antigen in the prostate, these transgenic mice were able to mount a cytotoxic immune response against PSA expressed by tumor cells, indicating that expression of the transgene has not resulted in complete nonresponsiveness. This transgenic mouse model will provide a well defined system to gain an insight into the mechanisms of nonresponsiveness to PSA, ultimately leading to strategies for immunotherapy of human prostate cancer using PSA as the target antigen.

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“…Cumulative evidence for an autoimmune basis for CP/CPPS comes from animal models of experimental autoimmune prostatitis (EAP) that have proven to be reliable for the study of CP/CPPS and have provided important data about the immune mechanisms underlying disease induction, development, and pathological consequences (Table 1 ). EAP, non-infectious autoimmune animal models of CP/CPPS achieved by immunization of rats or mice with PAg plus adjuvants, have been studied since several decades ago ( 61 , 79 – 82 ). EAP models mirror the human disease showing its typical characteristics: the presence of IFNγ-secreting Th1 lymphocytes specific to PAg, increased levels of cytokines in semen, chronic pelvic pain, and associated prostate tissue inflammation and lesions ( 10 , 36 , 37 , 72 , 83 ).…”

Section: Possible Causes Of Cp/cppsmentioning

confidence: 99%

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

et al. 2017

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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain.

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Experimental Autoimmune Damage to Rat Male Accessory Glands. I. Transfer of Autoimmune Response by Spleen Cells

Cited by 21 publications

References 15 publications

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Treatment of Experimental Autoimmune Prostatitis in Nonobese Diabetic Mice by the Vitamin D Receptor Agonist Elocalcitol

Tissue-specific expression of the human prostate-specific antigen gene in transgenic mice: Implications for tolerance and immunotherapy

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

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