Inhibiting Interleukin-18 Production Through the Mitogen-Activated Protein Kinase Pathway, A Potential Role of Corticotr
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Inhibiting Interleukin-18 Production Through the Mitogen-Activated Protein Kinase Pathway, A Potential Role of Corticotropin-Releasing Hormone in Chronic Plaque Psoriasis Chun-Lei Zhou,1,2 Xiao-Jing Yu,1 Da-Xing Cai,1 Yong-Hao Xu,1 Chun-Yang Li,1,3 and Qing Sun1,3
Abstract—Corticotropin-releasing hormone (CRH) and CRH receptors (CRH-Rs) are expressed in the skin; CRH-R1 is the predominant receptor. Whether the CRH/CRH-R1 system plays a role in psoriasis has not yet been assessed. Immunohistochemistry, real-time RT-PCR, ELISA assay, and Western blot analysis were used to investigate the expression of CRH/CRH-R1 in patients with chronic plaque psoriasis and that of IL-18 in CRH-treated HaCaT cells. CRH and CRH-R1 were downregulated in patients with chronic plaque psoriasis. In vitro, CRH attenuated the expression of IL-18 by a mitogenactivated protein kinase signaling pathway through CRH-R1 in HaCaT cells. Thus, an aberrant cutaneous CRH/CRH-R1 system exists in lesions from chronic plaque psoriasis which might play a role in psoriasis and offers further evidence for the study of CRH in the skin. KEY WORDS: corticotropin-releasing hormone; interleukin-18; psoriasis; HaCaT cells; mitogen-activated protein kinase.
INTRODUCTION Psoriasis is considered a genetically programmed disease of dysregulated inflammation triggered by environmental stimuli, such as infections, medications, antigenic stimuli, and physical and/or emotional stress [11]. It is considered one of the best examples of the close relation between exacerbation and psychopathologic burden of patients. Indeed, clinical evidence supports that stress can influence the susceptibility and the progression of the disease [13, 27, 29]. 1
Department of Dermatology, Qilu Hospital, Shandong University, No 107 Wenhua Xi Road, Jinan, 250012, People’s Republic of China 2 Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, 250012, People’s Republic of China 3 To whom correspondence should be addressed at Department of Dermatology, Qilu Hospital, Shandong University, No 107 Wenhua Xi Road, Jinan, 250012, People’s Republic of China. E-mails: [email protected]; [email protected]
Corticotropin-releasing hormone (CRH) is produced mainly in the hypothalamus and regulates endocrine and behavioral responses to stress through the activation of the hypothalamic-pituitary-adrenal (HPA) axis, the main organizer of the body’s response to stress [15]. Endocrine stress responses also occur in peripheral tissue, outside of the classical HPA axis [19]. Recent research has indicated that CRH and CRH receptors (CRH-Rs) are expressed in the skin [33, 17, 32, 46], with CRH-R1 as the predominant receptor detected in human epidermis and dermis [23]. CRH-R1 mRNA expression in skin of psoriasis is lower than that in normal controls, which suggests that CRH/ CRH-R1 may be involved in the pathogenesis of psoriasis [37]. However, little is known about the exact me
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