PMID- 7512988
OWN - NLM
STAT- MEDLINE
DCOM- 19940520
LR  - 20220409
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 93
IP  - 4
DP  - 1994 Apr
TI  - Functional switching of macrophage responses to tumor necrosis factor-alpha (TNF 
      alpha) by interferons. Implications for the pleiotropic activities of TNF alpha.
PG  - 1661-9
AB  - Recent work conducted in our laboratory has been directed towards understanding 
      the role of TNF alpha in stimulating the synthesis of two macrophage gene 
      products, namely IGF-1, a growth factor implicated in wound repair and fibrosis, 
      and complement component factor B (Bf), an alternative pathway complement 
      component. The expression of these proteins is induced by hyaluronic acid and 
      poly (I:C), respectively, although TNF alpha plays a requisite role in the 
      expression of both proteins. The objective of this study was to determine the 
      mechanism governing the dichotomy in the expression of IGF-1 and Bf by TNF alpha. 
      First, we questioned if the diversity in IGF-1 and Bf synthesis was regulated at 
      the level of TNF receptor usage. Second, based on earlier findings that IFNs 
      contribute to the initiation of Bf expression, we determined if IFNs modulate the 
      response of macrophages to TNF alpha. Our data show that differences in TNF 
      receptor usage cannot fully explain the dichotomy in the expression of IGF-1 and 
      Bf. However, prior exposure to IFN-beta or IFN-gamma was found to be a dominant 
      factor controlling the expression of these proteins, suppressing IGF-1, and 
      enhancing Bf. These findings indicate that IFNs mediate a functional "switch" in 
      the response of macrophages to TNF alpha and suggest that the pattern of cytokine 
      expression by diverse macrophage stimuli is an important determinant of the 
      eventual responses of macrophages to TNF alpha.
FAU - Lake, F R
AU  - Lake FR
AD  - Department of Pediatrics, National Jewish Center for Immunology and Respiratory 
      Medicine, Denver, Colorado 80206.
FAU - Noble, P W
AU  - Noble PW
FAU - Henson, P M
AU  - Henson PM
FAU - Riches, D W
AU  - Riches DW
LA  - eng
GR  - HL-27353/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - 9008-11-1 (Interferons)
RN  - EC 3.4.21.47 (Complement Factor B)
RN  - O84C90HH2L (Poly I-C)
SB  - IM
MH  - Animals
MH  - Complement Factor B/biosynthesis
MH  - Hyaluronic Acid/pharmacology
MH  - Insulin-Like Growth Factor I/biosynthesis/genetics
MH  - Interferons/pharmacology/*physiology
MH  - Macrophages/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Poly I-C/pharmacology
MH  - RNA, Messenger/analysis
MH  - Receptors, Tumor Necrosis Factor/physiology
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/genetics/pharmacology/*physiology
PMC - PMC294209
EDAT- 1994/04/01 00:00
MHDA- 1994/04/01 00:01
PMCR- 1994/04/01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 1994/04/01 00:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
PHST- 1994/04/01 00:00 [pmc-release]
AID - 10.1172/JCI117148 [doi]
PST - ppublish
SO  - J Clin Invest. 1994 Apr;93(4):1661-9. doi: 10.1172/JCI117148.