TY - JOUR
T1 - Toll-like receptor signalling induces the expression of serum amyloid A in epidermal keratinocytes and dermal fibroblasts
AU - Morizane, S.
AU - Kajita, A.
AU - Mizuno, K.
AU - Takiguchi, T.
AU - Iwatsuki, Keiji
N1 - Funding Information:
We thank H. Katayama, T. Sunagawa, N. Iwata, S. Mishima, M. Kouro and T. Habu (Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences) for supporting our experiments. This work was partly supported by a grant from the Ministry of Health, Labour and Welfare (MHLW) (H23-Intractable Skin Disease-028) and a Grant-in-Aid for Young Scientists (B) (16K19724).
Publisher Copyright:
© 2018 British Association of Dermatologists
PY - 2019/1
Y1 - 2019/1
N2 - Background: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. Aim: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. Methods: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. Results: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. Conclusions: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.
AB - Background: Toll-like receptors (TLRs) play critical roles in innate immune response by sensing pathogen- or damage-associated molecular patterns. Epidermal keratinocytes and dermal fibroblasts also produce proinflammatory cytokines and chemokines under stimulation with TLR ligands. Serum amyloid A (SAA) is an essential factor in the pathogenesis of secondary amyloidosis, and also has immunomodulatory functions. SAA are produced mainly by hepatocytes but also by a variety of cells, including immune cells, endothelial cells, synoviocytes, and epidermal keratinocytes. However, SAA expression in human dermal fibroblasts has not been shown to date. Aim: To investigate the effect of TLR ligands on SAA expression in epidermal keratinocytes and dermal fibroblasts. Methods: We investigated whether TLR ligands induce the expression of SAA in normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) by real-time quantitative PCR and ELISA. The effect of SAA on its own expression in NHDFs was also studied. Results: SAA expression was induced via nuclear factor-κB by TLR1/2, 3, 5 and 2/6 ligands in NHEKs. In NHDFs, TLR1/2 and TLR2/6 ligands increased SAA expression. SAA further induced its own expression via TLR1/2 and NF-κB in NHDFs, as previously reported for NHEKs. Conclusions: Our results provide new evidence that the skin's innate immune response contributes to the production of SAA, which might lead to an increased risk of systemic complications such as secondary amyloidosis of recessive dystrophic epidermolysis bullosa.
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U2 - 10.1111/ced.13604
DO - 10.1111/ced.13604
M3 - Article
C2 - 29770468
AN - SCOPUS:85047466229
VL - 44
SP - 40
EP - 46
JO - Clinical and Experimental Dermatology
JF - Clinical and Experimental Dermatology
SN - 0307-6938
IS - 1
ER -