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Inhibition of benzalkonium chloride‐induced skin inflammation in mice by an indol‐1‐ylpropan‐2‐one inhibitor of cytosolic phospholipase A 2 α
Author(s) -
Roebrock K.,
Wolf M.,
Bovens S.,
Lehr M.,
Sunderkötter C.
Publication year - 2012
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2011.10637.x
Subject(s) - benzalkonium chloride , cytosol , phospholipase a2 , inflammation , phospholipase , phospholipase a , pharmacology , chemistry , medicine , biochemistry , enzyme , organic chemistry
Summary Background Irritant contact dermatitis (ICD) is a frequent and often underrated problem for which the major efficacious therapy is still local glucocorticoids, although they have known adverse effects due to their wide spectrum of action. A more focused therapeutic strategy would be the inhibition of a key enzyme for biosynthesis of the lipid mediators, cytosolic phospholipase A 2 α (cPLA 2 α), in ICD. We are analysing the pharmacological and biological effects of a selective cPLA 2 α inhibitor. Objectives To examine the usefulness of the potent and selective cPLA 2 α inhibitor 3‐(5‐carboxypentanoyl)‐1‐[3‐(4‐octylphenoxy)‐2‐oxopropyl]indole‐5‐carboxylic acid (compound 1) for therapy of inflammatory skin disorders. Methods We examined clinical and cellular effects of a selective cPLA 2 α inhibitor (compound 1) on ICD in mice. Results Topical application of the compound significantly reduced ear swelling after induction by the irritant benzalkonium chloride. Concomitantly, compound 1 inhibited the accumulation of granulocytes as well as the expression of inflammatory proteins such as tumour necrosis factor‐α, interleukin‐1β and macrophage inflammatory proteins 1α and 1β in the ear tissue. In primary murine keratinocytes, the benzalkonium chloride‐induced expression of these proteins was also downregulated after treatment with compound 1 in vitro . Conclusions Compound 1 is a well‐aimed agent for the treatment of nonspecific skin inflammation as it selectively inhibits cPLA 2 α and as it acts on an early stage of skin inflammation after its elicitation.