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Human 15-lipoxygenase-1 is a regulator of dendritic-cell spreading and podosome formation
Karolinska Univ, Huddinge Hosp, Ctr Hematol & Regenerat Med, Karolinska Inst,Dept Med, Stockholm, Sweden.;Karolinska Univ, Hosp Solna, Karolinska Inst, Dept Med,Div Hematol, Stockholm, Sweden..
Karolinska Univ, Hosp Solna, Karolinska Inst, Dept Med,Div Hematol, Stockholm, Sweden..
Karolinska Univ, Hosp Solna, Karolinska Inst, Dept Med,Div Hematol, Stockholm, Sweden..
Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
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2017 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 31, no 2, p. 491-504Article in journal (Refereed) Published
Abstract [en]

Dendritic cells (DCs) involved in proinflammatory immune responses derive mainly from peripheral monocytes, and the cells subsequently mature and migrate into the inflammatory micromilieu. Here we report that suppressing of 15-lipoxygenase-1 led to a substantial reduction in DC spreading and podosome formation in vitro. The surface expression of CD83 was significantly lower in both sh-15-lipoxygenase-1 (15-LOX-1)-transduced cells and DCs cultivated in the presence of a novel specific 15-LOX-1 inhibitor. The T-cell response against tetanus-pulsed DCs was only affected to a minor extent on inhibition of 15-LOX-1. In contrast, endocytosis and migration ability of DCs were significantly suppressed on 15-LOX-1 inhibition. The expression of 15-LOX-1 in DCs was also demonstrated in affected human skin in atopic and contact dermatitis, showing that the enzyme is indeed expressed in inflammatory diseases in vivo. This study demonstrated that inhibiting 15-LOX-1 led to an impaired podosome formation in DCs, and consequently suppressed antigen uptake and migration capacity. These results indicated that 15-LOX-1 is a potential target for inhibiting the trafficking of DCs to lymphoid organs and inflamed tissues and decreasing the inflammatory response attenuating symptoms of certain immunologic and inflammatory disorders such as dermatitis.-Han, H., Liang, X., Ekberg, M., Kritikou, J. S., Brunnstro " m, angstrom., Pelcman, B., Matl, M., Miao, X., Andersson, M., Yuan, X., Schain, F., Parvin, S., Melin, E., Sjoberg, J., Xu, D., Westerberg, L. S., Bjorkholm, M., Claesson, H.- E. Human 15-lipoxygenase- 1 is a regulator of dendritic-cell spreading and podosome formation.

Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL , 2017. Vol. 31, no 2, p. 491-504
Keywords [en]
arachidonic acid, cell migration, dermatitis, endocytosis
National Category
Medicinal Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-320760DOI: 10.1096/fj.201600679RRISI: 000394235400006PubMedID: 27825104OAI: oai:DiVA.org:uu-320760DiVA, id: diva2:1090954
Funder
Swedish Cancer SocietyLars Hierta Memorial FoundationThe Karolinska Institutet's Research FoundationAvailable from: 2017-04-25 Created: 2017-04-25 Last updated: 2018-01-13Bibliographically approved

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