Expression and function of pro‐inflammatory interleukin IL‐17 and IL‐17 receptor in normal, benign hyperplastic, and malignant prostate

Steiner, Georg; Newman, Martin; Paikl, Doris; Stix, Ursula; Memaran, Nima; Lee, Chung; Marberger, Michael

doi:10.1002/pros.10238

Cited by 219 publications

(170 citation statements)

References 43 publications

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“…They showed that activated T cells in BPH tissue and in prostate cancer express high levels of IL17 (REF. 85). Further work to more fully elucidate the phenotypic and biological properties of all T-cell subsets in the prostate is required before we can understand the significance of acquired cellmediated immunity in prostate carcinogenesis.…”

Section: Immunobiology Of Prostate Inflammationmentioning

confidence: 99%

Inflammation in prostate carcinogenesis

et al. 2007

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About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease. NIH Public Access Author ManuscriptNat Rev Cancer. Author manuscript; available in PMC 2013 January 23. $watermark-text $watermark-text $watermark-textProstate cancer is the most common non-cutaneous malignant neoplasm in men in Western countries, responsible for the deaths of approximately 30,000 men per year in the United States 1 . The number of afflicted men is increasing rapidly as the population of males over the age of 50 grows worldwide. Therefore, finding strategies for the prevention of prostate cancer is a crucial medical challenge. As men in South East Asian countries have a low incidence of prostate cancer that increases rapidly after immigration to the West, this disease is not an intrinsic feature of ageing. The pathogenesis of prostate cancer reflects both hereditary and environmental components. What are the environmental factors and genetic variations that have produced such an epidemic of prostate cancer? Approximately 20% of all human cancers in adults result from chronic inflammatory states and/or chronic inflammation 2-4 (BOX 1), which are triggered by infectious agents or exposure to other environmental factors, or by a combination thereof. There is also emerging evidence that inflammation is crucial for the aetiology of prostate cancer. This evidence stems from epidemiological, histopathological and molecular pathological studies. The objective of this Review is to take a multidisciplinary approach to present and analyse such studies. Because several reviews related to these topics have been published [5][6][7] , here we will focus on new findings and ideas with the purpose of sparking innovative areas of investigation that might ultimately lead to the prevention of prostate cancer. Enigmas in the aetiology of prostate cancerAs in other cancers, prostate cancer develops through the accumulation of somatic genetic and epigenetic changes, resulting in the inactivation of tumour-suppressor genes and caretaker genes, and the activation of oncogenes 8,9 (TABLE 1). There is also evidence for an underlying genetic instability that might facilitate tumour progression 10,11 . Although these genetic and epigenetic changes are crucial for our understanding of 'how' prostate cancer arises, another key remaining question is 'why'...

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Section: Immunobiology Of Prostate Inflammationmentioning

confidence: 99%

Inflammation in prostate carcinogenesis

et al. 2007

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“…haematopoietic tumours in immunocompetent mice) [112,113] of tumours in experimental animals. Although the role of IL-17 in tumour biology is unclear and evidence remains conflicting, IL-17 can be detected in some (such as ovarian, skin and prostatic cancers) [114][115][116] but not all (e.g. acute myeloid leukaemia) [117] human tumours and one emerging theme is that, when present, it promotes angiogenesis [111,114], for example through the up-regulation of angiogenic factors such as CXCL1, CXCL5, CXCL6 and CXCL8 [118], thereby facilitating tumour growth and invasion.…”

Section: Systemic Lupus Erythematosis (Sle) and Other Conditionsmentioning

confidence: 99%

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Afzali

Lombardi

Lechler

et al. 2007

Clinical and Experimental Immunology

655

470

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“…Indeed, as testosterone lymphocytes progressively accumulate, IL4 and IL13 expression increases, suggesting a shift toward a Th0/Th2 immune response (Steiner et al 2003a). There is also evidence that a loss of tolerance to self-antigens, associated with expansion of Th17 cells and IL17 overexpression, is crucial in BPH development (Steiner et al 2003b). This is also supported by the observation that IL8 and IL6, key executors of stromal growth in BPH, are produced by prostatic stromal cells in response to IL17 (Penna et al 2009), thus linking a self-perpetuating autoimmune response to altered tissue remodeling and hyperplastic growth (Ropiquet et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Vignozzi

Cellai²,

Santi³

et al. 2012

Journal of Endocrinology

127

107

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Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor a, lipopolysaccharide, or CD4 C T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4 C T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon g inducible protein 10, IP10), and Th2 (IL9)-and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-kB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

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Expression and function of pro‐inflammatory interleukin IL‐17 and IL‐17 receptor in normal, benign hyperplastic, and malignant prostate

Cited by 219 publications

References 43 publications

Inflammation in prostate carcinogenesis

Inflammation in prostate carcinogenesis

The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

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