NDLI: Interferon-γ Primes Intact Human Coronary Arteries and Cultured Coronary Smooth Muscle Cells to dsRNA and self-RNA Induced Inflammatory Responses by Upregulating TLR3 and MDA51

Content Provider	PubMed Central
Author	Ahmad, Usman Ali, Rahmat Lebastchi, Amir H. Qin, Lingfeng Lo, Sheng-fu L. Yakimov, Alexander O. Khan, Salman F. Choy, Jonathan C. Geirsson, Arnar Pober, Jordan S. George, Tellides
Abstract	Atherosclerosis of native coronary arteries and graft arteriosclerosis in transplanted hearts are characterized by activation of innate and adaptive immune responses. Nucleic acids generated by infections or cell death have been detected within arteriosclerotic lesions and it is known that microbial and synthetic nucleic acids evoke inflammatory responses in cultured vascular cells. Here we report that model RNA, but not DNA, instigated robust cytokine and chemokine production from intact human coronary arteries containing both intrinsic vascular cells and resident/infiltrating leukocytes. A ssRNA analogue induced tumor necrosis factor-α and IP-10 secretion by isolated human PBMC, but not vascular cells. Conversely, synthetic dsRNA induced these inflammatory mediators by vascular cells, but not PBMC. IFN-γ, a cytokine linked to atherosclerosis and graft arteriosclerosis, potentiated the inflammatory responses of intact arteries and cultured vascular smooth muscle cells (VSMCs) to poly(I:C) and was necessary for inflammatory responses of VSMC to self-RNA derived from autologous cells. IFN-γ also induced the expression of TLR3, MDA5, and RIG-I dsRNA receptors. siRNA knockdown revealed that TLR3 mediated VSMC activation by poly(I:C), whereas MDA5 was more important for VSMC stimulation by self-RNA. IFN-γ-mediated induction of dsRNA receptors and priming for inflammatory responses to poly(I:C) was confirmed in vivo using immunodeficient mice bearing human coronary artery grafts. These findings suggest that IFN-γ, and by inference adaptive immunity, sensitizes the vasculature to innate immune activators, such as RNA and activation of IFN-γ-primed vascular cells by exogenous or endogenous sources of RNA may contribute to the inflammatory milieu of arteriosclerosis.
Related Links	http://dx.doi.org/10.4049/jimmunol.0902283
Ending Page	1294
Page Count	12
Starting Page	1283
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	2
Volume Number	185
Language	English
Publisher Date	2010-07-15
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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