PMID- 10415057
OWN - NLM
STAT- MEDLINE
DCOM- 19990812
LR  - 20081121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 3
DP  - 1999 Aug 1
TI  - Regulation of macrophage chemokine expression by lipopolysaccharide in vitro and 
      in vivo.
PG  - 1537-44
AB  - The host response to Gram-negative LPS is characterized by an influx of
      inflammatory cells into host tissues, which is mediated, in part, by localized
      production of chemokines. The expression and function of chemokines in vivo
      appears to be highly selective, though the molecular mechanisms responsible are
      not well understood. All CXC (IFN-gamma-inducible protein (IP-10), macrophage
      inflammatory protein (MIP)-2, and KC) and CC (JE/monocyte chemoattractant protein
      (MCP)-1, MCP-5, MIP-1alpha, MIP-1beta, and RANTES) chemokine genes evaluated were
      sensitive to stimulation by LPS in vitro and in vivo. While IL-10 suppressed the 
      expression of all LPS-induced chemokine genes evaluated in vitro, treatment with 
      IFN-gamma selectively induced IP-10 and MCP-5 mRNAs, but inhibited LPS-induced
      MIP-2, KC, JE/MCP-1, MIP-1alpha, and MIP-1beta mRNA and/or protein. Like the
      response to IFN-gamma, LPS-mediated induction of IP-10 and MCP-5 was Stat1
      dependent. Interestingly, only the IFN-gamma-mediated suppression of LPS-induced 
      KC gene expression was IFN regulatory factor-2 dependent. Treatment of mice with 
      LPS in vivo also induced high levels of chemokine mRNA in the liver and lung,
      with a concomitant increase in circulating protein. Hepatic expression of
      MIP-1alpha, MIP-1beta, RANTES, and MCP-5 mRNAs were dramatically reduced in
      Kupffer cell-depleted mice, while IP-10, KC, MIP-2, and MCP-1 were unaffected or 
      enhanced. These findings indicate that selective regulation of chemokine
      expression in vivo may result from differential response of macrophages to pro-
      and antiinflammatory stimuli and to cell type-specific patterns of stimulus
      sensitivity. Moreover, the data suggest that individual chemokine genes are
      differentially regulated in response to LPS, suggesting unique roles during the
      sepsis cascade.
FAU - Kopydlowski, K M
AU  - Kopydlowski KM
AD  - Department of Microbiology and Immunology, Uniformed Services University of the
      Health Sciences, Bethesda, MD 20814, USA.
FAU - Salkowski, C A
AU  - Salkowski CA
FAU - Cody, M J
AU  - Cody MJ
FAU - van Rooijen, N
AU  - van Rooijen N
FAU - Major, J
AU  - Major J
FAU - Hamilton, T A
AU  - Hamilton TA
FAU - Vogel, S N
AU  - Vogel SN
LA  - eng
GR  - AI-18797/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Ccl12 protein, mouse)
RN  - 0 (Chemokines)
RN  - 0 (Chemokines, CC)
RN  - 0 (Chemokines, CXC)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (RNA, Messenger)
RN  - 130068-27-8 (Interleukin-10)
RN  - 82115-62-6 (Interferon-gamma)
SB  - AIM
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokines/antagonists & inhibitors/*biosynthesis/genetics
MH  - Chemokines, CC/antagonists & inhibitors/biosynthesis/genetics
MH  - Chemokines, CXC/antagonists & inhibitors/biosynthesis/genetics
MH  - Down-Regulation/immunology
MH  - Gene Expression Regulation/immunology
MH  - Injections, Intraperitoneal
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-10/physiology
MH  - Kinetics
MH  - Lipopolysaccharides/*administration & dosage/antagonists &
      inhibitors/*pharmacology
MH  - Macrophages, Peritoneal/*immunology/*metabolism
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Monocyte Chemoattractant Proteins/biosynthesis/genetics
MH  - RNA, Messenger/antagonists & inhibitors/biosynthesis
EDAT- 1999/07/22 00:00
MHDA- 1999/07/22 00:01
CRDT- 1999/07/22 00:00
PHST- 1999/07/22 00:00 [pubmed]
PHST- 1999/07/22 00:01 [medline]
PHST- 1999/07/22 00:00 [entrez]
AID - ji_v163n3p1537 [pii]
PST - ppublish
SO  - J Immunol. 1999 Aug 1;163(3):1537-44.