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  • Title: Expression and function of MIP-2 are reduced by dexamethasone treatment in vivo.
    Author: Schramm R, Liu Q, Thorlacius H.
    Journal: Br J Pharmacol; 2000 Sep; 131(2):328-34. PubMed ID: 10991927.
    Abstract:
    1. The objective of this study was to examine the effect of dexamethasone on tumour necrosis factor-alpha (TNF-alpha)-induced expression and function of macrophage inflammatory protein-2 (MIP-2) and neutrophil recruitment. For this purpose, we used air pouches raised on the dorsal skin of C57/B16 mice. 2. Initially, we examined the dose-response (0.01 - 0.5 microg ml(-1)) and kinetics (0 - 24 h) of TNF-alpha-induced leukocyte accumulation. The cellular response was maximal at 0.1 microg ml(-1) of TNF-alpha and 4 h after challenge and comprised more than 90% neutrophils. 3. Intraperitoneal (i.p.) pretreatment with 10 mg kg(-1) of dexamethasone for 2 h, but not 1 mg kg(-1), reduced TNF-alpha-induced recruitment of neutrophils by 87%. Administration of dexamethasone had no effect on the expression of CD18 on neutrophils. 4. TNF-alpha (0.1 microg ml(-1)) markedly increased the levels of MIP-2 in the air pouches 1 h after challenge and after 4 h the MIP-2 values returned to baseline. Notably, 2 h pretreatment with dexamethasone (10 mg kg(-1), i.p.) reduced MIP-2 expression by 65% in response to TNF-alpha (0.1 microg ml(-1)). On the other hand, dexamethasone treatment did not change the levels of interleukin-10 (IL-10) in the pouch exudate. 5. Administration of recombinant MIP-2 increased neutrophil accumulation at 0.5 and 1.0 microg ml(-1) after 4 h of challenge. Dexamethasone pretreatment for 2 h (10 mg kg(-1), i.p.) abolished the MIP-2-induced recruitment of neutrophils. 6. Taken together, our data demonstrate that dexamethasone may downregulate TNF-alpha-induced neutrophil recruitment by inhibiting both the expression and function of MIP-2 in vivo.
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