Activation of Nod1 and Nod2 induces innate immune responses of prostate epithelial cells.
BACKGROUND
Nod1 and Nod2 are cytosolic receptors which are responsible for sensing bacterial peptidoglycan derivatives. In this study, we determined whether Nod1 and Nod2 are involved in the innate immune responses of prostate epithelial cells.


METHODS
The expression of Nod1 and Nod2 was examined by RT-PCR and immunohistochemistry. ELISA was performed to determine the production of cytokines/chemokines. Activation of NF-κB and MAPK was examined using western blot analysis.


RESULTS
The Nod1 gene was distinctly expressed in all tested cells including DU145, PC3, and TRAMP-C2 cells, whereas Nod2 expression was weak. Both Nod1 and Nod2 proteins were expressed in normal mouse prostate epithelia with difference of expression levels. Tri-DAP (Nod1 agonist), but not MDP (Nod2), increased the production of IL-8 (or KC) and IL-6 in prostate epithelial cells. Tri-DAP and MDP could upregulate the gene expression of COX-2 and activate NF-κB and MAPK. In addition, Tri-DAP and MDP synergized with TLR agonists to induce the production of IL-8/KC or IL-6 in PC3 and TRAMP-C2 cells. We finally showed that Nod1 and Nod2 were also expressed in a wide range of prostate lesions including prostate intraepithelial neoplasm (PIN), phyllodes-like tumor, and adenocarcinoma in TRAMP (transgenic adenocarcinoma of the mouse prostate) mice, even though the expression level of Nod1 and Nod2 was different.


CONCLUSIONS
These results indicate that Nod1 and Nod2 may play important roles in the innate immune response of prostate epithelial cells and the development and progression of prostate cancer.
Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-711, Korea.
Min-Jung
MJ
Kang
Sook-Kyoung
SK
Heo
Eun-Jung
EJ
Song
Dong-Jae
DJ
Kim
Seung-Yun
SY
Han
Ju-Hee
JH
Han
Bo-Yeon
BY
Kim
Jong-Hwan
JH
Park
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism* / Q000502:physiology; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism* / Q000502:physiology; D011467:Prostate / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse