Wogonin suppresses TARC expression induced by mite antigen via heme oxygenase 1 in human keratinocytes. Suppressive effect of wogonin on mite antigen-induced TARC expression.
BACKGROUND
Mite antigen, extract from Dermatophagoides farinae in house dust, is a well-known causative agent of atopy or allergic diseases, which involves many inflammatory cytokines/chemokines expression. Heme oxygenase 1 (HO1) has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types.


OBJECTIVE
The aim of this study was to investigate the possible mechanism by which wogonin, a natural product isolated from Scutellaria baicalensis, inhibited the mite antigen-induced chemokine expression in human keratinocytes, HaCaT cells.


METHODS
The level of chemokine expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) and signaling study was performed by Western blot analysis.


RESULTS
The mite antigen-induced thymus- and activation-regulated chemokine (TARC/CCL17) expression in a dose-dependent manner via extracellular signal-regulated kinase (ERK) activation. However, it did not affect the expression of other chemokines including macrophage-derived chemokine (MDC/CCL22), RANTES, and IL-8. Interestingly, wogonin significantly suppressed the mite antigen-induced TARC expression via the induction of HO1. This suppression was completely restored by HO1 siRNA, suggesting a direct role of HO1 for the suppressive effect. Furthermore, exogenous CO, but not other end products of HO1 activity, also suppressed the mite antigen-induced TARC expression.


CONCLUSIONS
Wogonin induces HO1 expression, which in turn HO1 and/or CO suppresses TARC expression induced by mite antigen in human HaCaT cells.
Lee
Bok-Soo
BS
Medicinal Resources Research Institute, Department of Microbiology & Immunology, Wonkwang University School of Medicine, Iksan, Chonbuk 570-749, South Korea.
Shim
Sang Moo
SM
Heo
JungHee
J
Pae
Hyun-Ock
HO
Seo
Byeong Yun
BY
Han
Sang Youp
SY
Sohn
Dong-Hwan
DH
Jang
Seon-Il
SI
Chung
Hun-Taeg
HT
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology; D002461:Cell Line, Transformed; D054414:Chemokine CCL17; D019742:Chemokines, CC / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D040001:Dermatophagoides farinae; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D031364:Scutellaria baicalensis
D039741:Antigens, Dermatophagoides; C106230:CCL17 protein, human; D054414:Chemokine CCL17; D019742:Chemokines, CC; D004365:Drugs, Chinese Herbal; D044950:Flavanones; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; C085514:wogonin