Induction of macrophage inflammatory protein 2 gene expression by interleukin 1 beta in rat lung.
BACKGROUND
Recruitment of inflammatory cells in the lungs may contribute to tissue injury as a result of mediators released from these cells. Interleukin 1 beta (IL-1 beta) is a potent inducer of neutrophil accumulation, a process that may require local protein biosynthesis. Macrophage inflammatory protein 2 (MIP-2) is a approximately 6 kD heparin binding protein and is a member of the C-X-C superfamily that causes significant neutrophil chemotaxis and activation in vitro. A study was performed to determine whether IL-1 beta could induce the expression of MIP-2 in the lungs of Brown-Norway rats.


METHODS
rhIL-1 beta (500 U) or 0.9% NaCl was injected intratracheally and bronchoalveolar lavage (BAL) cells and lung tissues were evaluated for MIP-2 mRNA expression after RNA extraction by Northern blot analysis. MIP-2 probe was prepared from cDNA obtained by reverse transcriptase-polymerase chain reaction (RT-PCR) of BAL cells obtained from a rat treated with lipopolysaccharide.


RESULTS
There was no detectable MIP-2 mRNA in the lungs of control rats but a marked enhancement of the expression at four hours with no expression at 12 hours and a slight expression at 24 hours. IL-1 beta induced a significant influx of neutrophils into BAL fluid with a transient increase in macrophages. In situ hybridisation of lungs using MIP-2 cDNA probe labelled with digoxigenin showed expression of MIP-2 mRNA in airway mononuclear cells and airway epithelium at four hours after IL-1 beta; at 24 hours the signal had nearly gone.


CONCLUSIONS
IL-1 beta induces the expression of MIP-2 mRNA in rat lung. MIP-2 may be one chemokine that could contribute to IL-1 beta induced neutrophil influx.
Xu
W B
WB
Department of Thoracic Medicine, National Heart and Lung Institute, London, UK.
Haddad
E B
EB
Tsukagoshi
H
H
Adcock
I
I
Barnes
P J
PJ
Chung
K F
KF
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054426:Chemokine CXCL2; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000494:pharmacology*; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D015846:Monokines / Q000096:biosynthesis*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011914:Rats, Inbred BN
D054426:Chemokine CXCL2; D016207:Cytokines; D007375:Interleukin-1; D015846:Monokines; D012333:RNA, Messenger