Numerous GWAS reports have confirmed that several autophagy-related genetic variations, including ATG16L1
and IRGM, were closely associated with enhanced risk of IBD (25,26).
The tissue sections were stained by ATG16L1
(bs-4007R) and LC3C (bs-20416R) polyclonal antibodies purchased from Bioss [R] and visualized by LSAB System-HRP Dako (K0679).
Loss of the autophagy protein Atg16L1
enhances endotoxin-induced IL-1beta production.
Macrophages derived from ATG16L1
(autophagy-related 16-like 1)-knockout mice present with a defect in autophagy and exhibit a high production of IL-1p after LPS stimulation44.
Knockout of Atg16L1
led to increased amounts of inflammatory cytokines (IL-1[beta] and IL-18) in the presence of LPS stimulation.
Electron microscopy of Paneth cells in the mutant mice revealed a decreased number of secretory granules, a fragmented ER, and damaged mitochondria, which resembled the morphology of the Paneth cells deficient of autophagy mediator ATG16L1
or ATG5 .
Another variation that has been shown to have a strong relation with the disease is the T300A polymorphism in the ATG16L1
gene, which is involved in the occurrence of autophagosome (39).
who found that invasive bacteria induce autophagic responses via binding of bacterial NOD1 ligand to cellular NOD1 at the bacterial entry site, which then triggers autophagy by NOD1 binding to ATG16L1
, an autophagy-inducing protein.
Expression in carotid atherosclerotic plaques is associated with plaque vulnerability.
Antibodies were rabbit anti-IR-[beta], IRS2, LC3I and II, Atg3, Atg12, Atg16L1
, Bcl2, PI3Kp85 (1:500, CST, USA), and mouse anti-GAPDH (1:1000, Abcam, USA).
Hakonarson, "Classification of genetic profiles of Crohn's disease: a focus on the ATG16L1
gene," Expert Review of Molecular Diagnostics, vol.