2019 Fiscal Year Final Research Report
Function of Antimicrobial Peptide Cathelicidin in Psoriasis, Infections, and Metabolic Syndrome
| Project/Area Number |
19K21251
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| Project/Area Number (Other) |
18H06136 (2018)
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund (2019)
Single-year Grants (2018) |
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| Review Section |
0803:Pathology, infection/immunology, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2018-08-24 – 2020-03-31
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| Keywords | 乾癬 / メタボリック症候群 / カセリサイディン / DAMPs / LL-37 / 抗菌ペプチド |
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| Outline of Final Research Achievements |
We added poly(dA:dT) (mock dsDNA) and high mobility group box 1 protein (HMGB1), which are representative damage-associated molecular patterns (DAMPs) and known ligands of scavenger receptors, to human cultured keratinocytes (NHEKs) with or without active form of cathelicidin (LL-37). As a result，inflammatory cytokines such as IL-6 and TNF-α were more strongly induced than those LL-37 or DAMPs alone. In addition, immunohistochemistry using lesional skin from psoriasis patients revealed that IL-36γ was positive in the epidermis only in cases with a large number of LL-37-positive keratinocytes. These results suggest that LL-37 and its associated inflammation induce IL-36γ, which is important for the pathogenesis of psoriasis.
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| Free Research Field |
皮膚科学、免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
LL-37がDAMPsにより炎症誘導を強めることで，TNF-α，IL-36γといった乾癬のサイトカインを誘導し，その病態形成に関わることが示された。また，DAMPsは乾癬だけでなく広く炎症およびそれに伴う細胞傷害で放出されることが知られており、急性炎症性疾患である感染症や，慢性炎症を伴うメタボリック症候群でも同様の機序で炎症惹起を来している可能性が示された．過去にわれわれはLL-37とDAMPsによる炎症誘導の機序にスカベンジャー受容体が関与することを報告しており、LL-37やスカベンジャー受容体に対する抗体や薬剤が，新たな機序の抗炎症薬となる可能性を考えている．
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