10.6084/m9.figshare.1481219.v1
Lucía Sanjurjo
Lucía
Sanjurjo
Núria Amézaga
Núria
Amézaga
Mar Naranjo-Gómez
Mar
Naranjo-Gómez
Carolina Armengol
Carolina
Armengol
Maria-Rosa Sarrias
Maria-Rosa
Sarrias
Gemma Aran
Gemma
Aran
Lilibeth Arias
Lilibeth
Arias
Francesc E Borràs
Francesc
E Borràs
The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses
Taylor & Francis Group
2015
PIK
TNF secretion
lps
3c
1b
lta
LC 3 puncta
THP 1 macrophages
responses CD 5L
macrophage TNF inhibition
THP 1 macrophages overexpressing CD 5L
IL 10 secretion
CD 5L axis
CD 5L influences
CD 5L
monocytic THP 1 macrophages
novel autophagy inducer
surface molecules lipopolysaccharide
autophagy protein ATG 7
CD 5L activates PtdIns 3K
PtdIns 3K isoforms
Additional siRNA experiments
2015-03-04 00:00:00
Journal contribution
https://tandf.figshare.com/articles/journal_contribution/The_human_CD5L_AIM_CD36_axis_A_novel_autophagy_inducer_in_macrophages_that_modulates_inflammatory_responses/1481219
<div><p>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.</p></div>