Premium
Il‐1β‐induced post‐transition effect of NF‐kappaB provides time‐dependent wave of signals for initial phase of intrapostatic inflammation
Author(s) -
Vykhovanets Eugene V.,
Shukla Sanjeev,
MacLennan Gregory T.,
Vykhovanets Olena V.,
Bodner Donald R.,
Gupta Sanjay
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20916
Subject(s) - extravasation , prostate , chemokine , inflammation , medicine , receptor , leukocyte extravasation , stromal cell , endocrinology , tumor necrosis factor alpha , nf κb , immunology , cancer
OBJECTIVE Our previous findings have shown that systemic administration of interleukin (IL)‐1β induces up‐regulation of nuclear factor‐kappa B (NF‐κB) in mouse prostate tissue that may be responsible for leukocyte extravasation into prostate stroma. It has been hypothesized that NF‐κB plays a role in the development of prostatitis, and that NF‐κB activation might provide chemoattractive signals for leukocyte extravasation in the prostate. METHODS IL‐1β was administrated intravenously, alone or with dexamethasone (Dex), to separate groups of C57BL/6J mice. Expression of NF‐κB, chemoattractant receptors, and IL‐17F in the prostates of the two groups of mice at various time periods following treatment was evaluated and compared. RESULTS IL‐1β administration up‐regulated NF‐κB/p65 activity in the mouse prostate. IL‐1β administration promoted extravasation and accumulation of CD45+ mononuclear cells but not neutrophils in the mouse prostate stroma. IL‐1β 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‐1β 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‐κB inhibitor, resulted in significantly down‐regulated IL‐1β‐induced NF‐κB/p65 activity, as well as reduced expression of chemokine receptors and IL‐17F in mouse prostate tissue. CONCLUSION Systemic IL‐1β administration induces NF‐κB‐responsive genes to promote aberrant NF‐κB/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). Prostate 69:633–643, 2009. © 2009 Wiley‐Liss, Inc.