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Toll-like receptors (TLRs) are known to recognize not only pathogen-associated molecular patterns but also danger-associated molecular patterns. Recent studies have characterized the expression levels and functions of TLRs in human epidermal cells. However, the characteristics of TLR family members in human dermal fibroblasts have not been thoroughly studied. Therefore, the present study systematically investigated the expression levels of TLRs and their functional responses to each ligand in skin fibroblasts. All 10 TLRs are expressed in skin fibroblasts. Stimulation of skin fibroblasts with each TLR ligand resulted in an increase of the interleukin-6 (IL-6), IL-8 and matrix metalloproteinase-1 proteins, indicating that ≥ 9 TLRs in skin fibroblasts are functionally active. Furthermore, stimulating skin fibroblasts with TLR1/2, 3 and 4 ligands induced the phosphorylation of inhibitor of nuclear factor κBα and the active phosphorylation of extracellular-signal regulated kinase 1/2. The expression level of each TLR was much higher in fibroblasts compared to keratinocytes. In particular, the fold-increase in IL-6 and IL-8 mRNA levels upon exposure to a TLR1/2 ligand was much higher in fibroblasts compared to keratinocytes, which appears to reflect the difference in expression levels of TLR1 and 2 between fibroblasts and keratinocytes. Taken together, these results show that all 10 TLRs are constitutively expressed and functional (except TLR10) in skin fibroblasts and suggest that TLRs in skin fibroblasts may play an important role in the detection of and response to different classes of pathogens and danger signals.

With age, the dermal-epidermal junction (DEJ) becomes thinner and production of its protein components decreases; this may be associated with increased fragility and wrinkling of skin. Topical treatment with palmitoyl-Arg-Gly-Asp (PAL-RGD) improves facial wrinkles, skin elasticity and dermal density in humans. In the present study, the effect of PAL-RGD on expression of DEJ components, such as laminin and collagen, was assessed. Human HaCaT keratinocytes were treated with PAL-RGD. The protein expression levels of laminin-332, collagen IV and collagen XVII were examined by western blotting. Reverse transcription-quantitative PCR was used to analyze laminin subunit (LAM)A3, LAMB3, LAMC2, collagen type IV α 1 chain (COL4A1) and COL17A1 mRNA expression levels. Western blot analysis showed that the expression levels of proteins comprising the DEJ, including laminin α3, β3 and γ2 and collagen IV and XVII demonstrated a significant dose-dependent increase following PAL-RGD treatment. Furthermore, PAL-RGD treatment significantly enhanced LAMA3, LAMB3, LAMC2, COL4A1 and COL17A1 mRNA expression levels. PAL-RGD may enhance the DEJ by inducing the expression of laminin-332, collagen IV and collagen XVII. [ABSTRACT FROM AUTHOR]