title: Renal tubular fluid shear stress facilitates monocyte activation toward inflammatory macrophages.
abstract: Modified urinary fluid shear stress (FSS) induced by variations of urinary fluid flow and composition is observed in early phases of most kidney diseases. Recently, we reported that renal tubular FSS promotes endothelial cell activation and subsequent adhesion of human monocytes, thereby suggesting that changes in urinary FSS can induce the development of inflammation (Miravète M, Klein J, Besse-Patin A, Gonzalez J, Pecher C, Bascands JL, Mercier-Bonin M, Schanstra JP, Buffin-Meyer B, BBRC 407: 813-817, 2011). Here, we evaluated the influence of tubular FSS on monocytes as they play an important role in the progression of inflammation in nephropathies. Human renal tubular cells (HK-2) were exposed to FSS 0.01 Pa for 30 min or 5 h. Treatment of human THP-1 monocytes with the resulting conditioned medium (FSS-CM) modified the expression of macrophage differentiation markers, suggesting differentiation toward the inflammatory M1-type macrophage. The effect was confirmed in freshly isolated human monocytes. In contrast to endothelial cells, the activation of monocytes by FSS-CM did not require TNF-α. Cytokine array analysis of FSS-CM showed that FSS modified secretion of cytokines by HK-2 cells, particularly by increasing secretion of TGF-β and by decreasing secretion of C-C chemokine ligand 2 (CCL2). Neutralization of TGF-β or CCL2 supplementation attenuated the effect of FSS-CM on macrophage differentiation. Finally, FSS-injured HK-2 cells expressed and secreted early biomarkers of tubular damage such as kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin. In conclusion, changes in urinary FSS should now also be considered as potential insults for tubular cells that initiate/perpetuate interstitial inflammation.
authors.affiliation: INSERM U1048/I2MC-Equipe 12, 2Université Toulouse III Paul-Sabatier, Instituteof Metabolic and Cardiovascular Diseases, 1 Av. Jean Poulhès, Toulouse Cedex 4, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Miravète
authors.forename: Romain
authors.initials: R
authors.lastname: Dissard
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.forename: Julien
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Cécile
authors.initials: C
authors.lastname: Caubet
authors.forename: Christiane
authors.initials: C
authors.lastname: Pecher
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Bascands
authors.forename: Muriel
authors.initials: M
authors.lastname: Mercier-Bonin
authors.forename: Joost P
authors.initials: JP
authors.lastname: Schanstra
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Buffin-Meyer
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000378:metabolism; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology / Q000502:physiology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011991:Receptors, Virus / Q000378:metabolism; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014556:Urine / Q000502:physiology; D014563:Urodynamics / Q000502:physiology
chemical_list: D000209:Acute-Phase Proteins; D017077:Culture Media, Conditioned; D016207:Cytokines; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D014409:Tumor Necrosis Factor-alpha