Toll-like receptor family members in skin fibroblasts are functional and have a higher expression compared to skin keratinocytes

Yao,Cheng; Oh,Jang-Hee; Lee,Dong  Hun; Bae,Jung-Soo; Jin,Cheng  Long; Park,Chi-Hyun; Chung,Jin  Ho

doi:10.3892/ijmm.2015.2146

Toll-like receptor family members in skin fibroblasts are functional and have a higher expression compared to skin keratinocytes

Authors:
- Cheng Yao
- Jang-Hee Oh
- Dong Hun Lee
- Jung-Soo Bae
- Cheng Long Jin
- Chi-Hyun Park
- Jin Ho Chung
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Affiliations: Department of Dermatology, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
Published online on: March 18, 2015 https://doi.org/10.3892/ijmm.2015.2146
Pages: 1443-1450

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Abstract

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.

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