Effect of proinflammatory cytokines on the expression and regulation of human beta-defensin 2 in human dental pulp cells.
BACKGROUND
Although the expression of human beta-defensin-2 (hBD-2) in odontoblasts from human dental pulp (HDP) has been reported, the production of hBD-2 and its regulation remains poorly understood. The aim of this study was to investigate the effect of cytokines on the induction of hBD-2 and its signaling mechanisms in HDP cells.


METHODS
After stimulation with tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha), reverse-transcriptase polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay experiments were performed to evaluate the effects of these cytokines on the production of hBD-2.


RESULTS
TNF-alpha and IL-1 alpha synergistically increased hBD-2 messenger RNA levels, protein expression, and activity. The up-regulation of hBD-2 by cytokines was attenuated by pretreatment with inhibitors of PKC, JNK, p38, ERK MAPK, nuclear factor-kappaB, and adenosine monophosphate-activated protein kinase (AMPK).


CONCLUSIONS
These results suggest that TNF-alpha and IL-1 alpha up-regulate HBD-2 expression in HDP cells through the PKC, JNK MAPK, p38, ERK, NF-kappaB, and AMPK pathways. Thus, the induction of hBD-2 by proinflammatory cytokines might up-regulate the pulpal host immune defense system.
Kim
Young-Suk
YS
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, South Korea.
Min
Kyung-San
KS
Lee
Sang-Im
SI
Shin
Su-Jung
SJ
Shin
Kyoung-Seob
KS
Kim
Eun-Cheol
EC
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002461:Cell Line, Transformed; D016207:Cytokines / Q000502:physiology*; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000494:pharmacology / Q000502:physiology; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; C106641:DEFB4A protein, human; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D016328:NF-kappa B; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases