LOX-1 dependent overexpression of immunoglobulins in cardiomyocytes in response to angiotensin II.
LOX-1, a cell surface lectin-like receptor, is upregulated by oxidized low-density lipoprotein (ox-LDL) and angiotensin II (Ang II), and plays an important role in host defense. The specific C-type lectin domain on LOX-1 is essential for ox-LDL binding and internalization, generation of oxidant species and eliciting immune response. Here, we show that LOX-1 deletion alters genes that relate to immune response. Microarray (and qPCR) analysis of cardiac tissues showed downregulated expression of several immunoglobulins (Igk-V8, Igk-C, Igh-6, Igj, Ighg, Igh, and Igl-V1) in the LOX-1 knockout (KO) mice [p<0.05 vs. the wild-type (WT) mice]. The expression of these immunoglobulins was upregulated several-fold in the LOX-1 KO mice hearts when these mice were infused with Ang II (p<0.05, vs. WT mice). Importantly, cultured mouse HL-1 cardiomyocytes expressed these immunoglobulins, and pretreatment of cardiomyocytes with a specific anti-LOX-1 antibody enhanced the generation of immunoglobulins upon subsequent exposure to Ang II. These observations mirrored the data obtained from WT and LOX-1 KO mice hearts in the resting state and following Ang II infusion. This study provides first set of data on immunoglobulin expression in cardiac tissues of WT and LOX-1 KO mice and in cultured HL-1 cardiomyocytes, and demonstrates that LOX-1 inactivation leads to upregulation of immunoglobulins in cardiomyocytes upon challenge with Ang II.
Kang
Bum-Yong
BY
Department of Internal Medicine, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, 4301 West Markham St., Slot 532, Little Rock, AR 72205-7199, USA.
Hu
Changping
C
Prayaga
Sastry
S
Khaidakov
Magomed
M
Sawamura
Tatsuya
T
Seung
Ki-Bae
KB
Mehta
Jawahar L
JL
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation; D017353:Gene Deletion; D007109:Immunity / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D051127:Scavenger Receptors, Class E / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
D007136:Immunoglobulins; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; D000804:Angiotensin II