Poly I:C Induces Collective Migration of HaCaT Keratinocytes Via IL-8

Overview

Journal BMC Immunol

Publisher Biomed Central

Specialty Allergy & Immunology

Date 2017 Apr 26

PMID 28438134

Citations 22

Authors

Kazuhide Takada

Shihoko Komine-Aizawa

Naoko Hirohata

Quang Duy Trinh

Atsuyoshi Nishina

Hirokazu Kimura

Satoshi Hayakawa

Affiliations

Soon will be listed here.

Abstract

Background: Delayed wound healing reduces the quality of life (QOL) of patients. Thus, understanding the mechanism of wound healing is indispensable for better management. However, the role of innate immunity in wound healing is thus far unknown. Recently the involvement of TLR3 in wound healing has been evaluated. The systemic administration of polyriboinosinic-polyribocytidylic acid (poly I:C ; a substitute for viral dsRNA and a ligand of toll-like receptor 3), enhances wound healing in vivo. The aim of this study is to improve our understanding of the link between innate immunity and human wound healing, particularly in re-epithelialization.

Results: The present study showed that poly I:C significantly accelerated collective HaCaT cell migration in a scratch assay. Poly I:C also increased IL-8 and bFGF production, and anti-IL-8 antibodies significantly inhibited the migration caused by poly I:C. Human recombinant IL-8 also accelerated collective HaCaT cell migration. An immunofluorescence assay and enzyme-linked immunosorbent assay (ELISA) also revealed that poly I:C decreased E-cadherin protein levels and increased vimentin protein levels, and anti-IL-8 antibody reversed this effect. In contrast, nucleic/cytosolic protein ratios of Snail 1 were unchanged in all tested conditions.

Conclusion: Our findings demonstrated that poly I:C accelerated collective HaCaT cell migration via autocrine/paracrine secretions of IL-8 and the subsequent incomplete epithelial-mesenchymal transition (EMT). Our findings provide a new strategy for wound healing by regulating innate immune systems in re-epithelialization.

Citing Articles

TLR3 activation mediates partial epithelial-to-mesenchymal transition in human keratinocytes.

Schneider A, Feehan R, Sennett M, Wills C, Garner C, Cong Z Life Sci Alliance. 2024; 7(12).

PMID: 39348939 PMC: 11443013. DOI: 10.26508/lsa.202402777.

Molecular mechanisms of thalidomide effectiveness on COVID-19 patients explained: ACE2 is a new ΔNp63α target gene.

Monteonofrio L, Virdia I, Pozzi S, Quadri R, Amendolare A, Marzano F J Mol Med (Berl). 2024; 102(11):1371-1380.

PMID: 39294414 PMC: 11525293. DOI: 10.1007/s00109-024-02485-x.

Lipopolysaccharide Derived from Directly Promotes the Migration of Human Keratinocytes.

Inagawa H, Nishizawa T, Kohchi C, Soma G In Vivo. 2024; 38(5):2172-2178.

PMID: 39187364 PMC: 11363747. DOI: 10.21873/invivo.13680.

Electric fields reverse the differentiation of keratinocyte monolayer by down-regulating E-cadherin through PI3K/AKT/Snail pathway.

Wu C, Chen X, Huang W, Yang J, Zhang Z, Liu J Heliyon. 2024; 10(12):e33069.

PMID: 39022057 PMC: 11252959. DOI: 10.1016/j.heliyon.2024.e33069.

IL-8 (CXCL8) Correlations with Psychoneuroimmunological Processes and Neuropsychiatric Conditions.

Shkundin A, Halaris A J Pers Med. 2024; 14(5).

PMID: 38793070 PMC: 11122344. DOI: 10.3390/jpm14050488.

References

Lin Q, Fang D, Fang J, Ren X, Yang X, Wen F . Impaired wound healing with defective expression of chemokines and recruitment of myeloid cells in TLR3-deficient mice. J Immunol. 2011; 186(6):3710-7. DOI: 10.4049/jimmunol.1003007. View

Turley E, Veiseh M, Radisky D, Bissell M . Mechanisms of disease: epithelial-mesenchymal transition--does cellular plasticity fuel neoplastic progression?. Nat Clin Pract Oncol. 2008; 5(5):280-90. PMC: 2846172. DOI: 10.1038/ncponc1089. View

Kluwe J, Mencin A, Schwabe R . Toll-like receptors, wound healing, and carcinogenesis. J Mol Med (Berl). 2008; 87(2):125-38. PMC: 2791674. DOI: 10.1007/s00109-008-0426-z. View

Iocono J, Colleran K, Remick D, Gillespie B, Ehrlich H, Garner W . Interleukin-8 levels and activity in delayed-healing human thermal wounds. Wound Repair Regen. 2000; 8(3):216-25. DOI: 10.1046/j.1524-475x.2000.00216.x. View

Straino S, Di Carlo A, Mangoni A, De Mori R, Guerra L, Maurelli R . High-mobility group box 1 protein in human and murine skin: involvement in wound healing. J Invest Dermatol. 2008; 128(6):1545-53. DOI: 10.1038/sj.jid.5701212. View

Lee D, Du F, Chen S, Nakasaki M, Rana I, Shih V . Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment. J Invest Dermatol. 2015; 135(8):2012-2020. PMC: 4504759. DOI: 10.1038/jid.2015.119. View

Jiang W, Sanders A, Ruge F, Harding K . Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-γ and potential clinical implications. Exp Ther Med. 2012; 3(2):231-236. PMC: 3438606. DOI: 10.3892/etm.2011.402. View

Kariko K, Ni H, Capodici J, Lamphier M, Weissman D . mRNA is an endogenous ligand for Toll-like receptor 3. J Biol Chem. 2004; 279(13):12542-50. DOI: 10.1074/jbc.M310175200. View

Umbreit C, Flanjak J, Weiss C, Erben P, Aderhold C, Faber A . Incomplete epithelial-mesenchymal transition in p16-positive squamous cell carcinoma cells correlates with β-catenin expression. Anticancer Res. 2014; 34(12):7061-9. View

10.

Dasu M, Isseroff R . Toll-like receptors in wound healing: location, accessibility, and timing. J Invest Dermatol. 2012; 132(8):1955-8. DOI: 10.1038/jid.2012.208. View

11.

Bhartiya D, Sklarsh J, Maheshwari R . Enhanced wound healing in animal models by interferon and an interferon inducer. J Cell Physiol. 1992; 150(2):312-9. DOI: 10.1002/jcp.1041500214. View

12.

Bernard J, Cowing-Zitron C, Nakatsuji T, Muehleisen B, Muto J, Borkowski A . Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat Med. 2012; 18(8):1286-90. PMC: 3812946. DOI: 10.1038/nm.2861. View

13.

Voss A, Bode G, Kerkhoff C . Double-stranded RNA induces IL-8 and MCP-1 gene expression via TLR3 in HaCaT-keratinocytes. Inflamm Allergy Drug Targets. 2012; 11(5):397-405. DOI: 10.2174/187152812803251042. View

14.

Borkowski A, Kuo I, Bernard J, Yoshida T, Williams M, Hung N . Toll-like receptor 3 activation is required for normal skin barrier repair following UV damage. J Invest Dermatol. 2014; 135(2):569-578. PMC: 4289479. DOI: 10.1038/jid.2014.354. View

15.

Bennett G, Dealey C, Posnett J . The cost of pressure ulcers in the UK. Age Ageing. 2004; 33(3):230-5. DOI: 10.1093/ageing/afh086. View

16.

Vitorino P, Meyer T . Modular control of endothelial sheet migration. Genes Dev. 2008; 22(23):3268-81. PMC: 2600767. DOI: 10.1101/gad.1725808. View

17.

Portou M, Baker D, Abraham D, Tsui J . The innate immune system, toll-like receptors and dermal wound healing: A review. Vascul Pharmacol. 2015; 71:31-6. DOI: 10.1016/j.vph.2015.02.007. View

18.

Olaru F, Jensen L . Chemokine expression by human keratinocyte cell lines after activation of Toll-like receptors. Exp Dermatol. 2010; 19(8):e314-6. PMC: 2891305. DOI: 10.1111/j.1600-0625.2009.01026.x. View

19.

Piccinini A, Midwood K . DAMPening inflammation by modulating TLR signalling. Mediators Inflamm. 2010; 2010. PMC: 2913853. DOI: 10.1155/2010/672395. View

20.

Rorth P . Collective cell migration. Annu Rev Cell Dev Biol. 2009; 25:407-29. DOI: 10.1146/annurev.cellbio.042308.113231. View