title: IL-1α modulates neutrophil recruitment in chronic inflammation induced by hydrocarbon oil.
abstract: Exposure to naturally occurring hydrocarbon oils is associated with the development of chronic inflammation and a wide spectrum of pathological findings in humans and animal models. The mechanism underlying the unremitting inflammatory response to hydrocarbons remains largely unclear. The medium-length alkane 2,6,10,14 tetramethylpentadecane (also known as pristane) is a hydrocarbon that potently elicits chronic peritonitis characterized by persistent infiltration of neutrophils and monocytes. In this study, we reveal the essential role of IL-1α in sustaining the chronic recruitment of neutrophils following 2,6,10,14 tetramethylpentadecane treatment. IL-1α and IL-1R signaling promote the migration of neutrophils to the peritoneal cavity in a CXCR2-dependent manner. This mechanism is at least partially dependent on the production of the neutrophil chemoattractant CXCL5. Moreover, although chronic infiltration of inflammatory monocytes is dependent on a different pathway requiring TLR-7, type I IFN receptor, and CCR2, the adaptor molecules MyD88, IL-1R-associated kinase (IRAK)-4, IRAK-1, and IRAK-2 are shared in regulating the recruitment of both monocytes and neutrophils. Taken together, our findings uncover an IL-1α-dependent mechanism of neutrophil recruitment in hydrocarbon-induced peritonitis and illustrate the interactions of innate immune pathways in chronic inflammation.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Tolga
authors.initials: T
authors.lastname: Barker
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Osamu
authors.initials: O
authors.lastname: Takeuchi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D002908:Chronic Disease; D006838:Hydrocarbons / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000502:physiology*; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D009821:Oils / Q000494:pharmacology*; D010847:Picolines / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: C524030:1-(3-picolinium)-12-triethylammonium-dodecane dibromide; D006838:Hydrocarbons; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D009821:Oils; D010847:Picolines; D017472:Receptors, Interleukin-1