Il‐1β‐induced post‐transition effect of NF‐kappaB provides time‐dependent wave of signals for initial phase of intrapostatic inflammation

Abstract

Our previous findings have shown that systemic administration of interleukin (IL)-1 beta induces up-regulation of nuclear factor-kappa B (NF-kappaB) in mouse prostate tissue that may be responsible for leukocyte extravasation into prostate stroma. It has been hypothesized that NF-kappaB plays a role in the development of prostatitis, and that NF-kappaB activation might provide chemoattractive signals for leukocyte extravasation in the prostate. IL-1 beta was administrated intravenously, alone or with dexamethasone (Dex), to separate groups of C57BL/6J mice. Expression of NF-kappaB, chemoattractant receptors, and IL-17F in the prostates of the two groups of mice at various time periods following treatment was evaluated and compared. IL-1 beta administration up-regulated NF-kappaB/p65 activity in the mouse prostate. IL-1 beta administration promoted extravasation and accumulation of CD45+ mononuclear cells but not neutrophils in the mouse prostate stroma. IL-1 beta administration provided earlier (4 hr) CXCR1/IL-8RA receptor expression in mouse prostate as a first signal, inducing capillary homing, adhesion, and initial extravasation of mononuclear cells into the prostate tissue. IL-1 beta administration also induced relatively late (24 hr) up-regulation of VCAM1 in the endothelial cells of microvessels and of IL-17F in prostate epithelium and in stromal infiltrating leukocytes. Concomitant administration of Dex, a known NF-kappaB inhibitor, resulted in significantly down-regulated IL-1 beta-induced NF-kappaB/p65 activity, as well as reduced expression of chemokine receptors and IL-17F in mouse prostate tissue. Systemic IL-1 beta administration induces NF-kappaB-responsive genes to promote aberrant NF-kappaB/p65 activity, which may be critical in the development of prostatitis through its role in the production of chemoattractant signals that promote extravasation and stromal accumulation of mononuclear cells (mainly by CXCR1/IL-8RA), and initiation of a new wave of pro-inflammatory signals favorable to chronic inflammation (mainly by IL-17F).