Characterisation of inflammatory cells in benign prostatic hyperplasia

Anim, Jehoram T.; Udo, Cheryl; John, Bency

doi:10.1016/s0065-1281(98)80040-8

Cited by 55 publications

(37 citation statements)

References 8 publications

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“…22 It is well known that normal prostate and BPH tissue often contain chronic inflammation, which can be extensive. 23,24 However, we did not observe any obvious correlation between FGF2-expressing cells detected by immunohistochemistry and infiltrates of chronic inflammatory cells, so the extent to which inflammation contributes to IL-8 and FGF2 expression in vivo is unclear. In addition, we do not know the extent to which the IL-8 produced by the epithelial cells is normally released onto the stroma or whether inflammation and atrophy may increase such release.…”

mentioning

confidence: 59%

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Giri

Ittmann

2001

The American Journal of Pathology

119

103

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Benign prostatic hyperplasia (BPH) is an extremely common disease of older men in which there is benign overgrowth of the prostatic transition zone, leading to obstruction of urine outflow. Fibroblast growth factor (FGF) 2, a potent growth factor for prostatic stromal and epithelial cells, is increased twofold in BPH and its concentration is correlated with stromal proliferation in this condition. Immunohistochemistry of normal and hyperplastic prostate revealed that FGF2-expressing stromal cells were present in higher numbers near the epithelial acini, implying that epithelial cells may express a factor that induces FGF2 expression by stromal cells. Benign prostatic hyperplasia (BPH) is an extremely common condition of older men, such that by 70 years of age the majority of men exhibit clinical symptoms of this disease. 1 The benign growth of the prostatic transition zone that is characteristic of BPH leads to obstruction of urine outflow and in this manner causes considerable morbidity. Thus BPH is of considerable medical importance and yet its pathogenesis is still obscure.Prostate growth is controlled by a variety of polypeptide growth factors, including members of the fibroblast growth factor (FGF) gene family. 2 FGF2, FGF7, and FGF9 are all present in high concentrations in normal human prostate. 3-6 FGF2 is a potent growth factor for prostatic stromal cells. 4,6,7 In addition it can stimulate proliferation of primary prostatic epithelial cells in culture. 5,6 Thus FGF2 can act as both a paracrine growth factor for prostatic epithelial cells and as an autocrine growth factor for prostatic stromal cells.The concentration of both FGF7 4 and FGF2 3,4 are significantly increased in hyperplastic prostate in comparison to normal peripheral and transition zone tissue. FGF2 is a potent mitogen for prostatic stromal cells and quantitative analysis of cellular proliferation by Ki67 immunohistochemistry of frozen sections of the tissue taken before protein extraction revealed a correlation between increased FGF2 tissue concentration and increased proliferation of stromal cells in BPH tissue, 4 consistent with a key role for this growth factor in driving the abnormal stromal proliferation in BPH.Given that FGF2 protein is increased in BPH and that this overexpression has functional consequences for the proliferation of prostatic stromal cells, we sought to determine what factors control FGF2 expression in the human prostate. We report here that interleukin (IL)-8 is produced by prostatic epithelial cells and can act as a paracrine inducer of FGF2 production by prostatic stromal cells in vitro. In addition, we have found that IL-8 is present in substantial quantities in human prostate in vivo and that IL-8 concentration is elevated in BPH tissue. Thus stromal proliferation in BPH is controlled, at least in part, by IL-8 secreted by prostatic epithelial cells. This may ultimately lead to increased tissue mass in the prostatic transition zone, which is critical in the pathogenesis of BPH. Materials and Methods Tissue Acq...

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mentioning

confidence: 59%

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Giri

Ittmann

2001

The American Journal of Pathology

119

103

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“…A study by Kohnen and Drach (1979) reported that 98% of analyzed BPH specimens showed signs of an inflammatory process. We and others demonstrated that the largest portion of BPH tissue infiltrating leukocytes are T lymphocytes (Anim et al, 1998;Bierhoff et al, 1996;McClinton et al, 1990;Steiner et al, 1994;Theyer et al, 1992), in particular, activated CD4 ϩ memory T lymphocytes (Steiner et al, 1994). Furthermore, it could be shown that BPH tissues and T cell lines contain considerable amounts of IFN-␥, IL-2, and IL-4 mRNA, and proliferation experiments suggested that these lymphokines may alter the growth of prostatic stromal cells (Kramer et al, 2002).…”

mentioning

confidence: 79%

Cytokine Expression Pattern in Benign Prostatic Hyperplasia Infiltrating T Cells and Impact of Lymphocytic Infiltration on Cytokine mRNA Profile in Prostatic Tissue

Steiner

Stix

Handisurya

et al. 2003

Laboratory Investigation

164

108

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SUMMARY:The aim of the study is to characterize the type of immune response in benign prostatic hyperplasia (BPH) tissue.BPH tissue-derived T cells (n ϭ 10) were isolated, activated (PMA ϩ ionomycin), and analyzed for intracellular reactivity with anti-IFN-␥ and IL-2, -4, -5, -6, -10, and -13, as well as TNF-␣ and -␤ by four-color flow cytometry. Lymphokine release was tested using Th1/Th2 cytokine bead arrays. The amount of IFN-␥ and IL-2, -4, -13, and TGF-␤ mRNA expressed in normal prostate (n ϭ 5) was compared with that in BPH tissue separated into segments with normal histology (n ϭ 5), BPH histology with (n ϭ 10) and without (n ϭ 10) lymphocytic infiltration, and BPH nodules (n ϭ 10). Expression of lymphokine receptors was analyzed by immunohistology, flow cytometry, and RT-PCR. We found that 28 Ϯ 18% of BPH T helper cells were IFN-␥ ϩ /IL-4 Ϫ Th1 cells, 10 Ϯ 2% were IFN-␥ Ϫ /IL-4 ϩ Th2, and 12 Ϯ 6% were IFN-␥ ϩ /IL-4 ϩ Th0 cells. In relation, cytotoxic and double-negative BPH T lymphocytes showed a slight decrease in Th1 and Th0 in favor of Th2. In double-positive BPH T lymphocytes, the trend toward Th2 (35 Ϯ 15%) was significant (Th1: 12 Ϯ 7%; Th0: 5 Ϯ 4%). Lymphokine release upon stimulation was found in the case of IL-2, IL-5, IFN-␥, and TNF-␣ Ͼ 4 g; of IL-4 Ͼ 2 g; and of IL-10 Ͼ 1 g/ml. Expression of lymphokine mRNA in tissue was increased (2-to 10-fold) in infiltrated BPH specimens with and without BPH histology. The infiltrated BPH specimens with normal histology differed from those with BPH histology, most evident by the significant decrease in IFN-␥ and the increase in TGF-␤ mRNA expression. Infiltrated BPH specimens with BPH histology expressed significantly more IFN-␥ (5-fold), IL-2 (10-fold), and IL-13 (2.8-fold) when compared with noninfiltrated BPH specimens. BPH nodules, however, showed the highest level of expression of IL-4 and IL-13, with only intermediate levels of IFN-␥ and very low levels of IL-2 mRNA. Immune response in histologically less transformed BPH specimens is primarily of type 1, whereas in chronically infiltrated nodular BPH and especially within BPH nodules, it is predominantly of type 0 or type 2. (Lab Invest 2003, 83:1131-1146.

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“…Although the use of autoantibody profiling in BPH has not been reported, observations have shown that the majority of BPH tissues demonstrate significantly increased T-lymphocyte infiltration. 9,10,11 In addition, Mahapokai et al 12 have reported that in a hormonallyinduced BPH canine model, hyperplasia was followed by cell-mediated and humoral immune responses. Finally, using expression microarrays and prostate tissues from symptomatic and asymptomatic BPH samples, Prakash et al 13 demonstrated that there is strong correlation between inflammation and symptomatic BPH.…”

Section: Reverse-capture Autoantibody Platform For Identification Of mentioning

confidence: 99%

A Comprehensive Approach Toward Novel Serum Biomarkers for Benign Prostatic Hyperplasia: The MPSA Consortium

et al. 2008

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Purpose-Clinical benign prostatic hyperplasia (BPH) is primarily diagnosed based on a diverse array of progressive lower urinary tract symptoms (LUTS) and is likely distinct from histological BPH, which is detected by the presence of non-malignant proliferation of prostate cells but may or may not be associated with symptoms. Pharmacological management of LUTS has emerged as an effective initial treatment for clinical BPH due to the introduction of new drug therapies shown to be effective in recent large clinical trials. Despite advances in symptom management and research into BPH pathology, diagnostic strategies for prediction of BPH progression and response to drug modalities are lacking and questions remain as to the molecular differences underlying clinical (symptomatic) versus histological (non-symptomatic) BPH. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-To date the MPSA has identified a number of promising biomarkers and other molecular and cellular changes associated with BPH. NIH Public AccessConclusions-These findings and ongoing consortium discovery efforts have the potential to provide a greater understanding of the defects underlying disease pathology and may lead to the development of early and more effective pharmacological treatment strategies for BPH.

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Characterisation of inflammatory cells in benign prostatic hyperplasia

Cited by 55 publications

References 8 publications

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Interleukin-8 Is a Paracrine Inducer of Fibroblast Growth Factor 2, a Stromal and Epithelial Growth Factor in Benign Prostatic Hyperplasia

Cytokine Expression Pattern in Benign Prostatic Hyperplasia Infiltrating T Cells and Impact of Lymphocytic Infiltration on Cytokine mRNA Profile in Prostatic Tissue

A Comprehensive Approach Toward Novel Serum Biomarkers for Benign Prostatic Hyperplasia: The MPSA Consortium

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