Table 1:
The role of eCIRP in inflammatory diseases.
| Inflammatory diseases |
eCIRP’s source |
eCIRP’s effects on cells/tissues | Inflammatory/ injury markers assessed |
Therapeutic outcomes of targeting eCIRP | References |
|---|---|---|---|---|---|
| sepsis | blood, monocyte, macrophage, liver, heart, lungs | macrophage, lymphocyte, neutrophil, EC, hepatocyte, lung, spleen, kidney | ALT, LDH, TNFα, IL-6, HMGB1, Th1 cell, CD69+ and CD25+ T cell, ICAM-1+ neutrophil, NETs, iNOS, RM neutrophil, NE, JAM-C, histology, apoptosis, E-selectin, ICAM-1, creatinine, BUN, NGAL, KIM-1 | CIRP−/− mice, anti-CIRP Ab and C23 reduce inflammatory cytokines, chemokines, activated immune cells, NETs, and iNOS and improve survival. TLR4−/− mice attenuate eCIRP-induced lymphocyte activation | 11, 13, 14, 15, 22 |
| hemorrhage | blood, macrophage, liver, heart | blood, macrophage, EC, liver, lung | ALT, AST, LDH, TNFα, IL-6, IL-1β, HMGB1, MPO, histology, EC barrier, ICAM-1 | CIRP−/− mice, anti-CIRP Ab and C23 reduce inflammatory markers, MPO,
histology, ICAM-1, EC barrier and improve survival |
11, 23 |
| alcohol-induced brain inflammation | microglial cell, brain | blood, brain | ALT, AST, LDH, TNFα, IL-1β | CIRP−/− mice have reduced levels of ALT, AST, LDH, TNFα, and IL-1β | 19 |
| cerebral ischemia and reperfusion | microglial cell, brain | microglial cell, neuroblastoma cell, brain | TNFα, caspase, Bcl2, NF-κB | CIRP−/− mice have reduced infarct size and volume, less AIF1 expression in microglia | 21 |
| hepatic ischemia and reperfusion | blood | blood, liver | ALT, AST, LDH, histology, IL-6, MIP-2, neutrophils (Gr-1), apoptosis, iNOS, Cox-2 | anti-CIRP Ab reduces ALT, AST, LDH, IL-6, MIP-2, iNOS, Cox-2, neutrophils, apoptosis, and improves survival | 26 |
| ALI | recombinant CIRP injection | EC, lung | TNFα, IL-1β, ICAM-1, L-selectin, NAD(P)H oxidase, ROS, Nlrp3, ASC, casp-1, EC leakage, pyroptosis, BiP, pIRE1α, sXBP1 | CIRP−/− mice have reduced ER stress in lung | 17, 20 |
| sepsis-induced ALI | lung | blood, arterial EC, lung | AST, IL-6, IL-1β, MIP-2, KC, MPO, histology, apoptosis, BiP, pIRE1α, sXBP1, CHOP, c-Casp-12, CD31, NF-κB | CIRP−/− mice have reduced ER stress, NF-κB, IL-6, IL-1β, MIP-2, KC, MPO, histology, and apoptosis | 13, 14, 20 |
| renal I/R | blood, kidney | macrophage, blood, kidney | TNFα, IL-6, IL-1β, KC, NGAL, KIM-1, BUN, creatinine, histology, apoptosis, neutrophils, nitrotyrosine, Cox-2 | CIRP−/− mice, anti-CIRP Ab and C23 attenuate BUN, creatinine, inflammatory and injury markers and improve survival | 25, 48 |
| fracture trauma and hemorrhage (two hits) | blood | macrophage, lung | mtDNA fragmentation, apoptosis, ROS, autophagy, necroptosis | TLR4−/− and MyD88−/− mice protect against CIRP-induced mtDNA fragmentation | 18 |
| intestinal I/R | blood | blood, small intestine, lung | AST, LDH, TNFα, IL-6, histology, apoptosis, casp-3, MIP-2, MPO, Ly6G+ PMN | CIRP−/− mice, C23 attenuate IL-6, LDH, histology, apoptosis, casp-3, and MPO | 24, 65 |
| RA | blood, synovial fluid, monocyte | blood, synovial fluid | ESR, CRP, IL6, TNFα | not studied | 51, 52 |
| COPD | airway epithelial cell | epithelial cells | IL-1β, TNFα, MUC5AC, MAPK | CIRP siRNA attenuates cold-induced expression of IL-1β, TNFα, MUC5AC, and MAPK | 16 |
| UC | colon mucosa | colon | histology, F4/80 cell, apoptosis, TNF, IL-1, IL-17, IL-23, BCL2, BCLXL, Sox2, tumor size | CIRP−/− mice show less colonic inflammation, small tumor size and apoptosis | 53, 54 |
Abbreviations: EC, endothelial cells; ALT, alanine aminotransferase; LDH, lactate dehydrogenase; TNF, tumor necrosis factor; IL, interleukin; HMGB1, high mobility group box 1; ICAM-1, intercellular adhesion molecule-1; NETs, neutrophil extracellular traps; eCIRP, extracellular cold-inducible RNA-binding protein; iNOS, inducible nitric oxide synthase; TLR, Toll-like receptor; RM, reverse migrated; JAM-C, junctional adhesion molecule-C; NE, neutrophil elastase; BUN, blood urea nitrogen; NGAL, neutrophil gelatinase-associated lipocalin; KIM-1, kidney injury molecule-1; MPO, myeloperoxidase; MIP, macrophage inflammatory protein; NF-κB, nuclear factor-κB; Cox, cyclogenase; casp-3, caspase-3; PMN, polymorphonuclear neutrophils; mt, mitochondrial; NLRP3, NACHT, LRR and PYD domains-containing protein 3; ESR, erythrocyte sedimentation rate; CRP, c-reactive protein; MAPK, mitogen activated protein kinase; ALI, acute lung injury; I/R, ischemia/reperfusion; RA, rheumatoid arthritis; COPD, chronic obstructive pulmonary disease; UC, ulcerative colitis.