Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate.
BACKGROUND
Exposure of male Wistar rats to estradiol-17beta (E(2)) in the presence or absence of dihydrotestosterone propionate (DHT) was previously shown to result in prostate inflammation. The present study examines, for the first time, changes in the expression level of several proinflammatory genes during the course of this experimentally induced prostatitis.


METHODS
Adult male Wistar rats were given chronic exposure to E(2) + DHT by capsule implantation or were injected with E(2) for short-term exposure. Semiquantitative RT-PCR was employed to measure changes in proinflammatory transcript levels in the separated lobes of the prostate after various times of exposure to estrogen with or without DHT.


RESULTS
We observed an upregulation of IL-1beta, IL-6, MIP-2, and inducible nitric oxide synthase (iNOS) after only 4 days treatment with E(2). After 4 weeks of treatment with E(2) + DHT, a significant increase in transcript levels of IL-4, IL-5, IL-6, MIP-2, eotaxin, and iNOS was detected, while IL-1beta and TNF-alpha transcript levels only increased slightly. No increase in transcript levels for cyclooxygenase-2 (cox-2), IFN-gamma, IL-2, or IL-12 was observed.


CONCLUSIONS
Upregulation of proinflammatory transcripts occurred shortly after exposure to E(2) and well before any inflammatory cells were observed in the prostate. The pattern of gene expression resembled a T(H)2-type helper-cell response.
Harris
M T
MT
Department of Biology, Tufts University, Medford, Massachusetts 02155, USA.
Feldberg
R S
RS
Lau
K M
KM
Lazarus
N H
NH
Cochrane
D E
DE
D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000032:analysis*; D004247:DNA / Q000737:chemistry; D017931:DNA Primers / Q000737:chemistry; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000633:toxicity; D004195:Disease Models, Animal; D004958:Estradiol / Q000008:administration & dosage / Q000633:toxicity*; D005786:Gene Expression Regulation; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D007375:Interleukin-1 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D019001:Nitric Oxide Synthase / Q000032:analysis; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011472:Prostatitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D012313:RNA / Q000737:chemistry / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C515458:Ccl11 protein, rat; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D017931:DNA Primers; D007375:Interleukin-1; D015848:Interleukin-5; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D013196:Dihydrotestosterone; D015847:Interleukin-4; D004958:Estradiol; D012313:RNA; D004247:DNA; D019001:Nitric Oxide Synthase