PMID- 8751967
OWN - NLM
STAT- MEDLINE
DCOM- 19961210
LR  - 20190723
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 107
IP  - 3
DP  - 1996 Sep
TI  - Inhibitors of sphingolipid synthesis modulate interferon (IFN)-gamma-induced 
      intercellular adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR 
      expression on cultured normal human keratinocytes: possible involvement of 
      ceramide in biologic action of IFN-gamma.
PG  - 336-42
AB  - To elucidate the participation of sphingosine and ceramide in the biologic action 
      of cytokines on epidermal keratinocytes, we studied whether inhibitors of 
      sphingolipid synthesis modulate interferon (IFN)-gamma-induced intercellular 
      adhesion molecule (ICAM)-1 and human leukocyte antigen (HLA)-DR expression on 
      cultured normal human keratinocytes. Pretreatment of keratinocytes with 
      L-cycloserine or fumonisin B1, but not 
      1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP), significantly suppressed 
      both ICAM-1 and HLA-DR expression induced by IFN-gamma. Because the synthesis of 
      all kinds of sphingolipids is blocked by L-cycloserine and all except that of 
      sphinganine by fumonisin B1, whereas PDMP inhibits the synthesis of 
      glucosylceramide and glycosphingolipids, the result suggests the participation of 
      ceramide and/or sphingosine in IFN-gamma-induced ICAM-1 and HLA-DR expression. 
      Exogenous C2-ceramide reversed the effects of L-cycloserine and fumonisin B1. On 
      the other hand, sphingosine reversed the effect of L-cycloserine, but not of 
      fumonisin B1. These results indicate that ceramide participates in this pathway, 
      as fumonisin B1, but not L-cycloserine, inhibits the synthesis of ceramide from 
      sphingosine. In addition, reverse transcriptase polymerase chain reaction showed 
      that L-cycloserine reduced the mRNA for ICAM-1, HLA-DR alpha, and HLA-DR beta 
      induced by IFN-gamma, and C2-ceramide and sphingosine antagonized the effect of 
      L-cycloserine. Furthermore, the degradation rate of fluorescent sphingomyelin 
      into ceramide in keratinocytes was increased by IFN-gamma, suggesting that 
      IFN-gamma activates sphingomyelin hydrolysis in keratinocytes. These observations 
      suggest the possible role of ceramide in IFN-gamma-induced ICAM-1 and HLA-DR 
      expression on keratinocytes. Ceramide may function as an endogenous modulator 
      mediating the cytokine signals in keratinocytes.
FAU - Wakita, H
AU  - Wakita H
AD  - Department of Dermatology, Hamamatsu University School of Medicine, Japan.
FAU - Nishimura, K
AU  - Nishimura K
FAU - Tokura, Y
AU  - Tokura Y
FAU - Furukawa, F
AU  - Furukawa F
FAU - Takigawa, M
AU  - Takigawa M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (Ceramides)
RN  - 0 (Fumonisins)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Molecular Probes)
RN  - 0 (Mycotoxins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sphingolipids)
RN  - 0 (Sphingomyelins)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 3ZZM97XZ32 (fumonisin B1)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 95IK5KI84Z (Cycloserine)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Ceramides/physiology
MH  - Cycloserine/antagonists & inhibitors/pharmacology
MH  - *Fumonisins
MH  - HLA-DR Antigens/genetics/*metabolism
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/genetics/*metabolism
MH  - Interferon-gamma/*pharmacology
MH  - Keratinocytes/*metabolism
MH  - Molecular Probes/genetics
MH  - Molecular Sequence Data
MH  - Mycotoxins/pharmacology
MH  - RNA, Messenger/antagonists & inhibitors/metabolism
MH  - Reference Values
MH  - Sphingolipids/*antagonists & inhibitors/biosynthesis
MH  - Sphingomyelins/metabolism
MH  - Sphingosine/pharmacology
EDAT- 1996/09/01 00:00
MHDA- 1996/09/01 00:01
CRDT- 1996/09/01 00:00
PHST- 1996/09/01 00:00 [pubmed]
PHST- 1996/09/01 00:01 [medline]
PHST- 1996/09/01 00:00 [entrez]
AID - S0022-202X(15)42675-2 [pii]
AID - 10.1111/1523-1747.ep12363279 [doi]
PST - ppublish
SO  - J Invest Dermatol. 1996 Sep;107(3):336-42. doi: 10.1111/1523-1747.ep12363279.