Lipoxins: Potential anti-inflammatory, proresolution, and antifibrotic mediators in renal disease

Abstract

Lipoxins are lipoxygenase-derived lipid mediators with both anti-inflammatory and proresolution properties that have been demonstrated in vivo and in vitro. The bioactivity profile of lipoxins in vitro suggests that they have therapeutic potential in acute renal failure and glomerulonephritis; predictions that have been borne out to date in experimental models of renal disease. We review recent developments on the molecular basis of lipoxin bioactions mediated through receptor crosstalk and the accumulating evidence that lipoxins may have potential as novel anti-inflammatory agents.

Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis

“…5S-HpETE acts as precursor for the formation of 5S-HETE and 6E,8Z,11Z,14Z-5- (LTA 4 ) [51,52]. Overall, the LOX pathway is relatively complex in that several eicosanoid production pathways are interlinked and synthesis of the LOs, for example, is 5-, 12-and 15-LOX dependent [53,54]. This is evident in the 5-LOX pathway, where synthesis of the lipoxins A 4 (LXA 4 ) and B 4 (LXB 4 ) requires 12-LOX activity [55,56].…”

Elevated Expressions of 15-Lipoxygenase and Lipoxin A4 in Children with Acute Poststreptococcal Glomerulonephritis

“…The parents or guardians of all enrolled children had signed their names on the informed consent to a protocol approved by the committee of ethics of our three hospitals. 4 and LTB 4 Whole blood samples were drawn into 5-ml tubes containing heparin and exposed to the calcium ionophore A23187 (50 mol/L; Sigma, St. Louis, MO) 37°C for 30 minutes. After stimulation, reactions were stopped with 5 volumes of ice-cold methanol.…”

“…3 Accumulating evidence demonstrates that lipoxins, which serve as endogenous braking signals that inhibit neutrophil recruitment and promote resolution of inflammation, are potential anti-inflammatory and prosolution mediators in several experimental renal injuries. 3,4 Maintaining the balance between lipoxin and leukotriene formation is likely to be a critical determinant of the resolution of inflammation. 4 Apart from lipoxins, another 15-lipoxygenase (15-LO) derivative, 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), has been also shown to antagonize the chemotactic action and glomerular synthesis of leukotriene B 4 (LTB 4 ) in rats, and therefore play an anti-inflammatory role in experimental glomerulonephritis.…”

“…3,4 Maintaining the balance between lipoxin and leukotriene formation is likely to be a critical determinant of the resolution of inflammation. 4 Apart from lipoxins, another 15-lipoxygenase (15-LO) derivative, 15-S-hydroxyeicosatetraenoic acid (15-S-HETE), has been also shown to antagonize the chemotactic action and glomerular synthesis of leukotriene B 4 (LTB 4 ) in rats, and therefore play an anti-inflammatory role in experimental glomerulonephritis. 5 However, the expressions of 15-LO and its products in human renal diseases remain unknown.…”

“…5 However, the expressions of 15-LO and its products in human renal diseases remain unknown. The present studies were therefore undertaken to find tempo-ral changes and a possible role of lipoxin A 4 (LXA 4 ) and 15-S-HETE in the course of APSGN in children.…”