title: Toll-like receptor 3 ligand polyinosinic:polycytidylic acid promotes wound healing in human and murine skin.
abstract: Toll-like receptors (TLRs) are pattern-recognition receptors and have a critical role in both innate and adaptive responses to tissue injury. Our previous study showed that wound healing was impaired in TLR3-deficient mice. In this study, we investigated the capacity of the TLR3 agonist polyriboinosinic-polyribocytidylic acid (poly(I:C)) to promote the healing of skin wounds in humans and mice. We found that topical application with poly(I:C) accelerated the closure of wounds in patients with laser plastic surgery. In a mouse model, topical application of poly(I:C) markedly enhanced re-epithelialization, granulation, and neovascularization required for wound closure. Further studies revealed that poly(I:C) treatment resulted in enhanced recruitment of neutrophils and macrophages in association with upregulation of a chemokine, macrophage inflammatory protein-2 (MIP-2/CXCL2), in the wounds. The effect of poly(I:C) was abolished in TLR3-deficient mice or by treatment with MIP-2/CXCL2-neutralizing antibodies. These results suggest a potential therapeutic value of the TLR3 activator poly(I:C) for wound healing.
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Youkun
authors.initials: Y
authors.lastname: Lin
authors.forename: Xialin
authors.initials: X
authors.lastname: Liu
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.forename: Sijian
authors.initials: S
authors.lastname: Wen
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Du
authors.forename: Tao
authors.initials: T
authors.lastname: Lu
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Su
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.forename: Shiyou
authors.initials: S
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Wen
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Su
mesh_terms: D000818:Animals; D054426:Chemokine CXCL2 / Q000096:biosynthesis; D018925:Chemokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007834:Lasers; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D011070:Poly I-C / Q000378:metabolism*; D012867:Skin / Q000473:pathology; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D054426:Chemokine CXCL2; D018925:Chemokines; D051196:Toll-Like Receptor 3; D011070:Poly I-C