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Macrophages and T-lymphocytes are known to accumulate in the white adipose tissue (WAT) of obese mice and humans, but the factors that cause this infiltration are not yet determined. Chemokines, which attract leukocytes to inflammatory sites, are candidates for this process. Macrophage inflammatory protein-1[alpha] (MIP-1[alpha]) expression is significantly elevated in WAT of obese mice and humans and positively correlates with fasting plasma insulin, but its potential role in leukocyte recruitment to WAT is unknown. MIP-1[alpha]-deficient, heterozygous, and wild-type mice were fed a Western diet (WD) for 16 wk. Plasma lipids, adipose tissue mass, energy expenditure, food intake, liver triglyceride content, and inflammatory cytokine expression were not different among genotypes. Gene expression of macrophage markers F4/80 and CD68, as well as T-lymphocyte marker CD3[epsilon] was increased in perigonadal WAT of obese WD-fed mice but was not influenced by MIP-1[alpha] expression level. Immunohistochemical analysis of WAT also showed no effect of MIP-1[alpha] on macrophage content. Two related chemokines, MIP-1[beta] and RANTES, had reduced expression in obese male MIP-1[alpha]-deficient mice compared with wild-type controls (P [less than or equal to] 0.05). In mice fed the WD for 6 wk, WAT macrophage content was unchanged; however, [CD.sup.8+] T-lymphocytes accumulated to a lesser extent in the MIP-1[alpha]-null mice. Therefore, expression of MIP-1[alpha], as well as that of MIP-1[beta] and RANTES, increases as a consequence of weight gain, but these chemokines may not be required for the recruitment of monocytes to WAT during diet-induced obesity in mice and may impact T-lymphocyte recruitment only at early time points after WD feeding. chemokine; adipose tissue macrophage; macrophage inflammatory protein-1[beta]; regulated upon activation, normal T cell expressed and secreted doi: 10.1152/ajpendo.00050.2010.

Background: SIG‐1273 is a novel cosmetic active that provides a broad spectrum of benefits to the skin. Considering the chronic skin exposure to pollution in urban areas, we sought to determine if SIG‐1273 could provide additional protection against skin aging by inhibiting pollutant‐induced cytotoxicity and inflammation. Objective: Determine if SIG‐1273 possesses antipollution properties in vitro and evaluate the potential anti‐aging benefits of Age IQ™ Night Cream clinically in human subjects. Methods: In vitro studies utilizing normal human epidermal keratinocytes (NHEKs), were co‐treated with urban dust (SRM 1649b) and SIG‐1273 (toxicity protection measured by MTS assay). A water‐soluble fraction of urban dust (UD‐WS) induces pro‐inflammatory cytokine release (IL‐8) from NHEKs (measured via ELISA). An 8‐week, 37‐subject clinical trial was performed with 0.05% SIG‐1273 formulated in Age IQ™ Night Cream and applied topically to assess its potential to reduce the appearance of aging. Results: In vitro studies using NHEKs demonstrate SIG‐1273 protects against urban dust‐induced cell toxicity, reducing cell death by 66% and concentration dependently inhibits UD‐WS‐induced IL‐8 production (IC50 = 20 nmol/L), outperforming niacinamide, ascorbic acid, and α‐tocopherol, commonly used actives in antipollution skin‐care products. Clinical assessment of Age IQ™ Night Cream shows it is effective in improving the appearance of facial skin aging including fine lines and wrinkles, skin texture, skin clarity/brightness, and firmness/elasticity. Conclusions: SIG‐1273, is demonstrated here for the first time to possess antipollution properties. Included as a key active ingredient in Age IQ™ Night Cream, this novel topical formulation provides benefits to individuals with aging skin. [ABSTRACT FROM AUTHOR]

Macrophage and T cell infiltration into metabolic tissues contributes to obesity-associated inflammation and insulin resistance (IR). C-C chemokine receptor 5 (CCR5), expressed on macrophages and T cells, plays a critical role in the recruitment and activation of proinflammatory M1 and TH1 immune cells to tissues and is elevated in adipose tissue (AT) and liver of obese humans and mice. Thus, we hypothesized that deficiency of CCR5 would protect against diet-induced inflammation and IR. CCR5-deficient (CCR5(-/-)) mice and C57BL/6 (WT) controls were fed 10% low-fat (LF) or 60% high-fat (HF) diets for 16 wk. HF feeding increased adiposity, blood glucose, and plasma insulin levels equally in both genotypes. Opposing our hypothesis, HF-fed CCR5(-/-) mice were significantly more glucose intolerant than WT mice. In AT, there was a significant reduction in the M1-associated gene CD11c, whereas M2 associated genes were not different between genotypes. In addition, HF feeding caused a twofold increase in CD4(+) T cells in the AT of CCR5(-/-) compared with WT mice. In liver and muscle, no differences in immune cell infiltration or inflammatory cytokine expression were detected. However, in AT and muscle, there was a mild reduction in insulin-induced phosphorylation of AKT and IRβ in CCR5(-/-) compared with WT mice. These findings suggest that whereas CCR5 plays a minor role in regulating immune cell infiltration and inflammation in metabolic tissues, deficiency of CCR5 impairs systemic glucose tolerance as well as AT and muscle insulin signaling.