Damage-associated molecular patterns in inflammatory bowel disease: From biomarkers to therapeutic targets

Table 1 Findings on the role of damage-associated molecular patterns in human and experimental inflammatory bowel diseases

DAMP	Human IBD	Experimental IBD
Calprotectin	Increased levels in the intestinal lumen and stools in both UC and CD[36,38,39]	-
Lactoferrin	Mostly correlates with colonic inflammation[41]	Beneficial therapeutic effects in colitis models[93,94]
Calreticulin	Related to inflammatory activity[44]	-
HMGB1	Increased levels in the stools of both adult and paediatric IBD patients[113]	Increased levels in DSS-induced colitis mice[52]
IL-1 alpha	Increased levels in the lamina propria of both UC and CD[59]	Associated with colonic inflammation initiation and amplification[60,61]
IL-33	Increased levels in the inflamed intestinal mucosa of IBD patients, especially in UC[66,67]	Increased levels in chemically induced colitis[66]; beneficial effects upon ST2 blockage[121]
ATP-P2X7	Overexpressed in IBD patients, particularly in CD[74]	Increases intestinal inflammation in chemically induced colitis[75]; P2X7-deficient mice essentially do not develop intestinal inflammation[74]
S 100 proteins	Increased faecal[95-98], mucosal[99], and serum[99-101] levels
HSPs	Increased levels[102-105]	Beneficial therapeutic effects in colitis models[106]
Galectins	Increased serum levels in UC and CD[107]	Galectins 1 and 2 show anti-inflammatory action[108,109]
		Galectin 4: Antibody blockage reduces inflammation[110]
Hyaluronan	ECM components accumulate in the colon of IBD patients[82], particularly in UC[115]	ECM components accumulate in experimental colitis tissues[83]

DAMPs: Damage-associated molecular patterns; IBD: Inflammatory bowel disease; CD: Crohn’s disease; UC: Ulcerative colitis; HSPs: Heat shock proteins; ECM: Extracellular matrix; IL: Interleukin; HMGB1: High-mobility group box 1.