PMID- 16784723
OWN - NLM
STAT- MEDLINE
DCOM- 20060911
LR  - 20181201
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 72
IP  - 4
DP  - 2006 Aug 14
TI  - Suppressive effects of antimycotics on tumor necrosis factor-alpha-induced CCL27, 
      CCL2, and CCL5 production in human keratinocytes.
PG  - 463-73
AB  - Antimycotic agents are reported to improve cutaneous symptoms of atopic 
      dermatitis or psoriasis vulgaris. Keratinocytes in these lesions excessively 
      produce chemokines, CCL27, CCL2, or CCL5 which trigger inflammatory infiltrates. 
      Tumor necrosis factor-alpha (TNF-alpha) induces production of these chemokines 
      via activating nuclear factor-kappaB (NF-kappaB). We examined in vitro effects of 
      antimycotics on TNF-alpha-induced CCL27, CCL2, and CCL5 production in human 
      keratinocytes. Antimycotics ketoconazole and terbinafine hydrochloride suppressed 
      TNF-alpha-induced CCL27, CCL2, and CCL5 secretion and mRNA expression in 
      keratinocytes in parallel to the inhibition of NF-kappaB activity while 
      fluconazole was ineffective. Anti-prostaglandin E2 (PGE2) antiserum or antisense 
      oligonucleotides against PGE2 receptor EP2 or EP3 abrogated inhibitory effects of 
      ketoconazole and terbinafine hydrochloride on TNF-alpha-induced NF-kappaB 
      activity and CCL27, CCL2, and CCL5 production, indicating the involvement of 
      endogenous PGE2 in the inhibitory effects. Prostaglandin H2, a precursor of PGE2 
      can be converted to thromboxane A2. Ketoconazole, terbinafine hydrochloride and 
      thromboxane A2 synthase (EC 5.3.99.5) inhibitor, carboxyheptyl imidazole 
      increased PGE2 release from keratinocytes and reduced that of thromboxane B2, a 
      stable metabolite of thromboxane A2. Carboxyheptyl imidazole also suppressed 
      TNF-alpha-induced NF-kappaB activity and CCL27, CCL2, and CCL5 production. These 
      results suggest that ketoconazole and terbinafine hydrochloride may suppress 
      TNF-alpha-induced NF-kappaB activity and CCL27, CCL2, and CCL5 production by 
      increasing PGE2 release from keratinocytes. These antimycotics may suppress 
      thromboxane A2 synthesis and redirect the conversion of PGH2 toward PGE2. These 
      antimycotics may alleviate inflammatory infiltration in atopic dermatitis or 
      psoriasis vulgaris by suppressing chemokine production.
FAU - Kanda, Naoko
AU  - Kanda N
AD  - Department of Dermatology, Teikyo University School of Medicine, 11-1, Kaga-2, 
      Itabashi-Ku, Tokyo 173-8605, Japan. nmk@med.teikyo-u.ac.jp
FAU - Watanabe, Shinichi
AU  - Watanabe S
LA  - eng
PT  - Journal Article
DEP - 20060619
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antifungal Agents)
RN  - 0 (CCL27 protein, human)
RN  - 0 (CCL5 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL27)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CC)
RN  - 0 (NF-kappa B)
RN  - 0 (Naphthalenes)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (PTGER2 protein, human)
RN  - 0 (PTGER3 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Prostaglandin E)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - 0 (Receptors, Prostaglandin E, EP3 Subtype)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 57576-52-0 (Thromboxane A2)
RN  - G7RIW8S0XP (Terbinafine)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - R9400W927I (Ketoconazole)
SB  - IM
MH  - Antifungal Agents/pharmacology
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics
MH  - Chemokine CCL27
MH  - Chemokine CCL5
MH  - Chemokines/*genetics
MH  - Chemokines, CC/genetics
MH  - Dinoprostone/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Keratinocytes/cytology/*drug effects/metabolism
MH  - Ketoconazole/*pharmacology
MH  - Male
MH  - NF-kappa B/genetics/metabolism
MH  - Naphthalenes/pharmacology
MH  - Oligonucleotides, Antisense/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Prostaglandin E/genetics/physiology
MH  - Receptors, Prostaglandin E, EP2 Subtype
MH  - Receptors, Prostaglandin E, EP3 Subtype
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Terbinafine
MH  - Thromboxane A2/metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2006/06/21 09:00
MHDA- 2006/09/12 09:00
CRDT- 2006/06/21 09:00
PHST- 2006/03/10 00:00 [received]
PHST- 2006/04/26 00:00 [revised]
PHST- 2006/05/01 00:00 [accepted]
PHST- 2006/06/21 09:00 [pubmed]
PHST- 2006/09/12 09:00 [medline]
PHST- 2006/06/21 09:00 [entrez]
AID - S0006-2952(06)00266-8 [pii]
AID - 10.1016/j.bcp.2006.05.001 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2006 Aug 14;72(4):463-73. doi: 10.1016/j.bcp.2006.05.001. Epub 
      2006 Jun 19.