Roxithromycin downmodulates Th2 chemokine production by keratinocytes and chemokine receptor expression on Th2 cells: its dual inhibitory effects on the ligands and the receptors.
Roxithromycin (RXM), an anti-bacterial macrolide, has various immunomodulatory activities. To investigate the ability of RXM to downregulate skin-infiltration of T-lymphocytes, we examined the effects of RXM on keratinocyte production of chemokines and T cell expression of chemokine receptors. Normal human and HaCaT keratinocytes were cultured with RXM and stimulants. RXM at 1 or 10 microM significantly suppressed the production/expression of Th2 chemokines MDC and TARC in these keratinocytes, but the production of IP-10 was not affected. The effect of RXM on T-cell expression of the corresponding chemokine receptors was also tested in Th2-rich peripheral blood lymphocytes. The IL-2-enhanced expression level of Th2 chemokine receptor CCR4 was decreased by RXM at 10 microM, whereas the expression of CXCR3 was unchanged. Thus, RXM downmodulates both the production and receptor expression of Th2 but not Th1 chemokines involved in cutaneous immunity, suggesting its beneficial therapeutic effects on Th2-mediated or allergic skin disorders.
Kobayashi
Miwa
M
Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. miw-koba@med.uoeh-u.ac.jp
Shimauchi
Takatoshi
T
Hino
Ryosuke
R
Tokura
Yoshiki
Y
D002460:Cell Line; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D019742:Chemokines, CC / Q000096:biosynthesis; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D008024:Ligands; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism*; D015575:Roxithromycin / Q000494:pharmacology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*
C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515354:CCR4 protein, human; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D018925:Chemokines; D019742:Chemokines, CC; D008024:Ligands; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015575:Roxithromycin