The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses
Copyright policy )The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses
CD5L (CD5 molecule-like) is a secreted glycoprotein that participates in host response to bacterial infection. CD5L influences the monocyte inflammatory response to the bacterial surface molecules lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by inhibiting TNF secretion. Here we studied the intracellular events that lead to macrophage TNF inhibition by human CD5L. To accomplish this goal, we performed functional analyses with human monocytic THP1 macrophages, as well as with peripheral blood monocytes. Inhibition of phosphatidylinositol 3-kinase (PtdIns3K) reversed the inhibitory effect of CD5L on TNF secretion. Among the various PtdIns3K isoforms, our results indicated that CD5L activates PtdIns3K (whose catalytic subunit is termed PIK3C3), a key modulator involved in autophagy. Further analysis revealed a concomitant enhancement of autophagy markers such as cellular LC3-II content, increased LC3 puncta, as well as LC3-LysoTracker Red colocalization. Moreover, electron microscopy showed an increased presence of cytosolic autophagosomes in THP1 macrophages overexpressing CD5L. Besides preventing TNF secretion, CD5L also inhibited IL1B and enhanced IL10 secretion. This macrophage anti-inflammatory pattern of CD5L was reverted upon silencing of autophagy protein ATG7 by siRNA transfection. Additional siRNA experiments in THP1 macrophages indicated that the induction of autophagy mechanisms by CD5L was achieved through cell-surface scavenger receptor CD36, a multiligand receptor expressed in a wide variety of cell types. Our data represent the first evidence that CD36 is involved in autophagy and point to a significant contribution of the CD5L-CD36 axis to the induction of macrophage autophagy.
CD36 Antigens, Lipopolysaccharides, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, peripheral blood monocytes, autophagy-related 7, PI3K, Monocytes, Phosphatidylinositol 3-Kinases, AIM, PIK3C3, Amines, RNA, Small Interfering, PBS, Cells, Cultured, oxLDL, GAPDH, interleukin, lipopolysaccharide, phosphoinositide 3-kinase, FCS, M, polyclonal antibody, Basic Research Paper, Recombinant Proteins, CD, macrophages, catalytic subunit type 3, lipoteichoic acid, glyceraldehyde 3-phosphate dehydrogenase, LTA, monocyte, 3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)- lysyl-(S)-lysyl-(S)-lysine (Pam3CysSer[Lys]4), ATG7, Microtubule-Associated Proteins, CD5 molecule-like, LPS, cluster of differentiation, PB monocytes, FSL1, macrophage, phosphate-buffered saline, Catalysis, poAb, CD5L, v-akt murine thymoma viral oncogene homolog, nuclear factor of kappa light polypeptide gene enhancer in B-cells, Autophagy, Humans, MAP1LC3A, Gene Silencing, RNA, Messenger, 3-MA, albumin, Inflammation, pam2CGDPKHPKSF, microtubule-associated protein 1 light chain 3, oxidized low-density lipoprotein, AKT, Macrophages, 3-methyladenine, IL, moAb, ALB, Integrin alphaV, MAPK, NFKB, Teichoic Acids, B (LC3), Microscopy, Electron, Microscopy, Fluorescence, monoclonal antibody, Pam3CSK4 (N-palmitoyl-S-[2, toll-like receptor, fetal calf serum, CD36
CD36 Antigens, Lipopolysaccharides, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, peripheral blood monocytes, autophagy-related 7, PI3K, Monocytes, Phosphatidylinositol 3-Kinases, AIM, PIK3C3, Amines, RNA, Small Interfering, PBS, Cells, Cultured, oxLDL, GAPDH, interleukin, lipopolysaccharide, phosphoinositide 3-kinase, FCS, M, polyclonal antibody, Basic Research Paper, Recombinant Proteins, CD, macrophages, catalytic subunit type 3, lipoteichoic acid, glyceraldehyde 3-phosphate dehydrogenase, LTA, monocyte, 3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-(S)-seryl-(S)-lysyl-(S)- lysyl-(S)-lysyl-(S)-lysine (Pam3CysSer[Lys]4), ATG7, Microtubule-Associated Proteins, CD5 molecule-like, LPS, cluster of differentiation, PB monocytes, FSL1, macrophage, phosphate-buffered saline, Catalysis, poAb, CD5L, v-akt murine thymoma viral oncogene homolog, nuclear factor of kappa light polypeptide gene enhancer in B-cells, Autophagy, Humans, MAP1LC3A, Gene Silencing, RNA, Messenger, 3-MA, albumin, Inflammation, pam2CGDPKHPKSF, microtubule-associated protein 1 light chain 3, oxidized low-density lipoprotein, AKT, Macrophages, 3-methyladenine, IL, moAb, ALB, Integrin alphaV, MAPK, NFKB, Teichoic Acids, B (LC3), Microscopy, Electron, Microscopy, Fluorescence, monoclonal antibody, Pam3CSK4 (N-palmitoyl-S-[2, toll-like receptor, fetal calf serum, CD36
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