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Macrophage migration inhibitory factor: a central regulator of wound healing.

ABSTRACT: Age-associated differences in estrogen levels critically modify the cutaneous wound healing response. Using a microarray-based approach, we profiled changes in gene expression within the wounds of mice that were wild type or null for the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in the presence or absence of estrogen. This experimental design identified more than 600 differentially expressed genes and established MIF as a key player in the wound healing process, regulating many novel repair/inflammation-associated gene targets. Moreover, MIF affected virtually all of the effects of reduced estrogen on wound repair. In humans, serum and wound levels of MIF increased with age and were strongly down-regulated by estrogen in vivo. Estrogen-regulated MIF transcription in vitro via a nuclear factor kappaB-dependent mechanism. These findings have wide-ranging implications for the many pathophysiological states in which MIF plays an important regulatory role and suggest a potential therapeutic role for MIF in modulating clinical conditions associated with age-related decline in estrogen levels.

SUBMITTER: Hardman MJ

PROVIDER: S-EPMC1613193 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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Macrophage migration inhibitory factor: a central regulator of wound healing.

Hardman Matthew J MJ Waite Alexander A Zeef Leo L Burow Matthew M Nakayama Toshinori T Ashcroft Gillian S GS

The American journal of pathology 20051201 6

Age-associated differences in estrogen levels critically modify the cutaneous wound healing response. Using a microarray-based approach, we profiled changes in gene expression within the wounds of mice that were wild type or null for the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in the presence or absence of estrogen. This experimental design identified more than 600 differentially expressed genes and established MIF as a key player in the wound healing process, regu ...[more]

PMID: 16314470

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Project description:Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes monocyte/macrophage-activation responses by increasing the expression of Toll-like receptors and inhibiting activation-induced apoptosis. On the basis of results of previous genetic linkage studies and reported altered innate immune response in autism spectrum disorder, we hypothesized that MIF could represent a candidate gene for autism spectrum disorder or its diagnostic components.Genetic association between autism spectrum disorder and MIF was investigated in 2 independent sets of families of probands with autism spectrum disorder, from the United States (527 participants from 152 families) and Holland (532 participants from 183 families). Probands and their siblings, when available, were evaluated with clinical instruments used for autism spectrum disorder diagnoses. Genotyping was performed for 2 polymorphisms in the promoter region of the MIF gene in both samples sequentially. In addition, MIF plasma analyses were conducted in a subset of Dutch patients from whom plasma was available.There were genetic associations between known functional polymorphisms in the promoter for MIF and autism spectrum disorder-related behaviors. Also, probands with autism spectrum disorder exhibited higher circulating MIF levels than did their unaffected siblings, and plasma MIF concentrations correlated with the severity of multiple autism spectrum disorder symptoms.These results identify MIF as a possible susceptibility gene for autism spectrum disorder. Additional research is warranted on the precise relationship between MIF and the behavioral components of autism spectrum disorder, the mechanism by which MIF contributes to autism spectrum disorder pathogenesis, and the clinical use of MIF genotyping.

Dataset Information

Macrophage migration inhibitory factor: a central regulator of wound healing.

Publications

Macrophage migration inhibitory factor: a central regulator of wound healing.

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