Toll-like receptor 4 (TLR4): new insight immune and aging

Kim, Hyo-Jin; Kim, Hyemin; Lee, Jeong-Hyung; Hwangbo, Cheol

doi:10.1186/s12979-023-00383-3

Immunity & Ageing

Table 1 TLR4 regulates age-related diseases

From: Toll-like receptor 4 (TLR4): new insight immune and aging

Organ	Control factor	Signaling pathway	Disease and symptom	Reference
Brain	DL0410	TLR4/MyD88/NF-κB signaling	Alzheimer’s disease BBB protection	[92]
	Tea polyphenol	TLR4/NF-κB signaling	Memory loss defense	[93]
	Naringin	TLR4/NF-κB signaling	Hippocampus recovery	[94]
	CAY10614 (TLR4 antagonist)	LPS/TLR4 signaling	Hippocampal cell senescence inhibition	[95]
	Probiotic combination	TLR4/NF-κB signaling	Hippocampus defense	[96]
	TLR4 antagonist	HMGB1/TLR4 signaling	Perioperative neurocognitive disorders (PNDs) recovery	[97]
	TDZD-8 (GSK-3β inhibitor)	TLR4 expression	BBB protection	[98]
Heart		HMGB1/TLR2, 4 signaling	Cardiac tissue aging	[99]
	HSP70	TLR4/NF-κB signaling	Deterioration of heart function (global I/R)	[100]
	Palmitate	TLR4, NLRP3 inflammasome	Cardiac fibroblasts progression	[101]
	NcoR1, HDAC1	TLR4/autophagy	Cardiac remodeling and contractile dysfunction	[102]
		TLR4 expression	Endothelial-dependent vascular relaxation inhibition	[103]
	Klotho	TLR4 signaling	Promoted differentiation of M2a/M2c macrophages improved myocardial viability	[104]
Adipose tissue	Fet A	TLR4 deficiency	Decreased inflammation Increased glucose tolerance	[105]
Pancreatic island		TLR4 deficiency	Decreased inflammation Protect insulin homeostasis	[106]
Adipocyte	SPARC	TLR4/IRF3 signaling	Increased inflammation protects metabolic function	[107]
Muscle		LPS/TLR4 signaling	Metabolic endotoxemia induction	[108]
Cartilage	DAP12	TLR4 signaling	Cartilage catabolism	[109]
Cartilage	PUM1	TLR4/NF-κB signaling	Chondrogenic potential of MSCs improvement	[110]
Lung		TLR4 expression	Alveoli collapse Lung volume expansion	[111]
Lung	HDAC2/p16^INK4a	TLR4 expression	Endothelial cell senescence Alveoli collapse Lung volume expansion	[112]
Blood	Lipoteichoic acid, Pam3CysK	TLR4/ TNF-α signaling	Sepsis inducement	[113]
Myeloma cell	DSUP/p53, p16	TLR4 signaling	Myeloma cell senescence	[114]
Placenta	Preeclampsia (PE)	TLR4, HH signaling	Placenta development, PMSC senescence	[115]
Bone marrow stromal cell	S100A9	TLR4 signaling, NLRP3 inflammasome	Cell senescence induction	[116]
Intestinal mucosa	Wheat oligopeptides	TLR4/Myd88/MAPK signaling	Intestinal barrier protection	[117]
Intestinal mucosa	Alginate oligosaccharide	TLR4/NF-κB signaling	Mucosal epithelial cell senescence, IMB maintainence	[118]
Skin	miR-326-3p	TLR4 expression	Skin cell senescence induction	[119]
Macrophage	cyto OH	OxPL/TLR4 signaling	Macrophage activation, Apoptosis promotion	[120]
Dental pulp cell	TLR4 neutralizing antibodies and inhibitor	TLR4/NF-κB signaling	Cell senescence inhibition	[121]

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