2,3-Dimethoxy-2'-hydroxychalcone ameliorates TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness via NF-kappaB inhibition and HO-1 induction in HaCaT cells.
Up-regulation of adhesion molecules plays an important role in the infiltration of leukocytes into the skin during the development of various inflammatory skin diseases, such as atopic dermatitis. In this study, we investigated the modulatory effects of 2,3-dimethoxy-2'-hydroxychalcone (DMHC) on tumor necrosis factor (TNF)-α-induced intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesiveness, as well as the molecular mechanisms underlying its action in the HaCaT human keratinocyte cell line. Pre-treating HaCaT cells with DMHC significantly suppressed TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness. DMHC inhibited TNF-α-induced activation of NF-κB. In addition, DMHC induced HO-1 expression as well as NRF2 activation. Furthermore, HO-1 knockdown using siRNA reversed the inhibitory effect of DMHC on TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that DMHC may inhibit TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes by suppressing the signaling cascades leading to NF-κB activation and inducing HO-1 expression in keratinocytes.
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
Hyejin
H
Kim
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
Gi Soo
GS
Youn
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
Soo Yeon
SY
An
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Korea.
Hyeok Yil
HY
Kwon
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
Soo Young
SY
Choi
Department of Biomedical Science and Research Institute for Bioscience & Biotechnology, Hallym University, Chuncheon 24252, Korea.
Jinseu
J
Park
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047188:Chalcones; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D051547:Heme Oxygenase-1; C013031:2'-hydroxychalcone