Role of interstitial inflammation in the pathogenesis of polycystic kidney disease

Abstract

The authors provide a comprehensive overview of our current understanding of the role of inflammation in the pathogenesis of polycystic kidney disease. In particular, the involvement of monocytes/macrophages and other infiltrating cells such as dendritic cells, T cells and other leukocytes are highlighted. ABSTRACT:Interstitial infiltrates, consisting of macrophages and other inflammatory cells, have been consistently reported in human and animal models of polycystic kidney diseases (PKD). However, the mechanisms underlying this inflammation are not well defined. Evidence suggests that interstitial inflammation in PKD is driven by pro-inflammatory chemoattractants such as monocyte chemoattractant protein-1 (MCP-1), and cytokines such as tumour necrosis factor (TNF)-a. Putative upregulated inflammatory pathways include JAK-STAT and nuclear factor (NF)-kB signalling. In addition, the genetic mutations of PKD may further complicate the relationship between inflammation and cystic disease, by increasing the susceptibility to inflammatory injury, and facilitating interactions between the genetically determined cystoproteins and biological mediators of inflammation. Moreover, the roles of interstitial inflammation in promoting cyst growth and progression to kidney failure in PKD are not clearly understood. Although anti-inflammatory therapies have attenuated cystogenesis in animal models, inflammatory cells may also have reparative actions. Thus, in developing therapies for PKD, it is prudent to consider the potential negative outcomes of ablating inflammation, and whether it is more viable to target certain inflammatory pathways over others.

Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats

“…Since NF-κB regulates the transcription of TNFa and CCL2 [17] , and as the cytokine products of these genes are commonly found in models of PKD [8] , we sought to…”

“…The non-canonical pathway is known to be stimulated by fewer stimuli (e.g., CD40 ligand and lymphotoxin-β2 [16] ) and usually implicates the RelB:p52 dimer in mediating lymphoid organ development [13,16] . There is an overlap between NF-κB-regulated genes and the pathophysiological features of PKD, such as inflammation (e.g., TNFa, CCL2), cell growth (e.g., cyclin D1), apoptosis (e.g., Bcl-xL) and hypertension (e.g., ANGII) [8,9,12,17,19] . These commonalities provide a theoretical basis for the involvement of NF-κB in PKD.…”

“…These genes encode proteins that are localized to the cilia of most cells within the body, including renal tubule epithelia [5,6] . Interstitial inflammation is a universal histological feature associated with renal cyst growth and formation [7][8][9] , and is possibly mediated by the release of pro-inflammatory cytokines from cyst-lining epithelial cells (CECs) [8] . Abnormalities in apoptosis and increased proliferation of CECs [7,10] , interstitial fibrosis [11] and hypertension [12] are also typical features of PKD.…”

Predictors of Autosomal Dominant Polycystic Kidney Disease Progression

“…Several other serum and laboratory factors have been associated with various aspects of ADPKD severity, including serum uric acid, HDL, fibroblast growth factor-23, collagenderived peptides, NGAL, IL-8, and TNFa. 78,[86][87][88][91][92][93][94] Although some of these factors may contribute to ADPKD progression, confirmation in additional studies is required as well as biomarker validation. …”

Resveratrol: A miraculous natural compound for diseases treatment

“…These mutations are initiator cysts formation and progression of disease (Zoja et al., 2014). Some of the pro‐inflammatory factors are identified in cyst fluid or urine samples of PKD patients (Ta, Harris, & Rangan, 2013). Recently, it has been shown that inflammation and cytokine signaling play a significant role in PKD pathogenesis.…”