Chemokine/chemokine receptor-mediated inflammation regulates pathologic changes from acute kidney injury to chronic kidney disease.
Ischemia-reperfusion injury is a main cause of acute kidney injury. Tubular necrosis and interstitial inflammatory cell infiltration are characteristic pathologic changes of acute kidney injury. The main necrotic area should be repaired with new tubular epithelial cells after the injury. On the other hand, some parts of the injured kidney progress to interstitial fibrosis, a characteristic pathologic change in chronic kidney disease. We hypothesized that interstitial infiltrating leukocytes, that are attracted and activated by chemokines, are key mediators in the pathogenesis of tubular necrosis, regeneration of the necrotic area, or interstitial fibrosis. A large number of chemokines were upregulated after ischemic injury, and chemokine receptor-expressing inflammatory cells were attracted by these chemokines. Genetic or molecular modulating experiments in the mouse model have begun to reveal the key participants and their specific roles at the levels of inflammation, regeneration, and fibrosis. Among these chemokines/chemokine receptors, our data indicated CCR2-mediated macrophage infiltration mainly affected tubular necrosis after ischemic acute kidney injury, interferon-gamma-inducible protein (IP)-10-producing macrophages participate in regeneration of tubular epithelial cells, and CX3CR1-mediated macrophages and platelet infiltration and aggregation play roles in interstitial fibrosis in chronic kidney disease. These chemokines and chemokine receptors on infiltrating inflammatory cells would be novel clinical markers or targets for therapeutic intervention.
Furuichi
Kengo
K
Division of Blood Purification, Kanazawa University Hospital, 13-1 Takara-machi, Kanazawa, Japan. kfuruichi@m-kanazawa.jp
Kaneko
Shuichi
S
Wada
Takashi
T
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018925:Chemokines / Q000378:metabolism*; D002908:Chronic Disease; D018450:Disease Progression; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007962:Leukocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D009336:Necrosis; D019707:Receptors, Chemokine / Q000378:metabolism*; D012038:Regeneration; D015427:Reperfusion Injury / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D019707:Receptors, Chemokine