PMID- 9449504
OWN - NLM
STAT- MEDLINE
DCOM- 19980205
LR  - 20141120
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 101
IP  - 1 Pt 1
DP  - 1998 Jan
TI  - Glucocorticoids inhibit chemokine generation by human eosinophils.
PG  - 75-83
AB  - Recent identification of eosinophils as a cellular source of various cytokines 
      suggests that eosinophil-derived cytokines contribute to allergic inflammation 
      through either an autocrine or a paracrine fashion. The profound inhibitory 
      effects of glucocorticoids (GCCs) on the production of various cytokines have 
      been well recognized, however, there has been no definitive evidence that GCCs in 
      fact inhibit cytokine generation by eosinophils. To verify the inhibitory ability 
      of GCCs on eosinophil cytokine generation, we studied the effect of GCCs by 
      determination of IL-8 and monocyte chemoattractant protein-1 (MCP-1) as 
      parameters. Dexamethasone (DEX) inhibited both generation and secretion of IL-8 
      in a dose-dependent fashion. DEX also dampened 
      formyl-methionyl-leucyl-phenylalanine-or ionomycin-induced eosinophil IL-8 
      production. Furthermore, MCP-1 production was also inhibited by DEX. The slope 
      and the shape of the dose-response curve of DEX were similar irrespective of 
      either the input stimuli or the output cytokines; half-maximal inhibition was 
      observed at 10(-8) mol/L, and nearly complete abolishment was observed at 10(-7) 
      mol/L. The competitive polymerase chain reaction for IL-8 mRNA and 
      semiquantitative polymerase chain reaction for MCP-1 mRNA revealed that the 
      inhibition occurred at a level of pretranslation. These results indicate that the 
      beneficial effect of GCCs in allergic inflammation might be related, at least in 
      part, to a direct effect of the drugs on eosinophil cytokine synthesis.
FAU - Miyamasu, M
AU  - Miyamasu M
AD  - Department of Medicine and Physical Therapy, University of Tokyo School of 
      Medicine, Japan.
FAU - Misaki, Y
AU  - Misaki Y
FAU - Izumi, S
AU  - Izumi S
FAU - Takaishi, T
AU  - Takaishi T
FAU - Morita, Y
AU  - Morita Y
FAU - Nakamura, H
AU  - Nakamura H
FAU - Matsushima, K
AU  - Matsushima K
FAU - Kasahara, T
AU  - Kasahara T
FAU - Hirai, K
AU  - Hirai K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokines)
RN  - 0 (DNA Primers)
RN  - 0 (Glucocorticoids)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 0 (Steroids)
RN  - 56092-81-0 (Ionomycin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 80295-54-1 (Complement C5a)
RN  - WI4X0X7BPJ (Hydrocortisone)
RN  - X4W7ZR7023 (Methylprednisolone)
SB  - IM
MH  - Base Sequence
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Chemokines/*biosynthesis/genetics
MH  - Complement C5a/pharmacology
MH  - DNA Primers/genetics
MH  - Dexamethasone/pharmacology
MH  - Eosinophils/*drug effects/*immunology
MH  - Gene Expression/drug effects
MH  - Glucocorticoids/*pharmacology
MH  - Humans
MH  - Hydrocortisone/pharmacology
MH  - In Vitro Techniques
MH  - Interleukin-8/biosynthesis/genetics
MH  - Ionomycin/pharmacology
MH  - Methylprednisolone/pharmacology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Polymerase Chain Reaction
MH  - RNA, Messenger/genetics/metabolism
MH  - Steroids/pharmacology
EDAT- 1998/02/04 00:00
MHDA- 1998/02/04 00:01
CRDT- 1998/02/04 00:00
PHST- 1998/02/04 00:00 [pubmed]
PHST- 1998/02/04 00:01 [medline]
PHST- 1998/02/04 00:00 [entrez]
AID - S0091-6749(98)70196-4 [pii]
AID - 10.1016/S0091-6749(98)70196-4 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 1998 Jan;101(1 Pt 1):75-83. doi: 
      10.1016/S0091-6749(98)70196-4.