scholarly journals Effect of 14-Membered-Ring Macrolides on Production of Interleukin-8 Mediated by Protease-Activated Receptor 2 in Human Keratinocytes

2008 ◽  
Vol 52 (4) ◽  
pp. 1538-1541 ◽  
Author(s):  
Tatsuya Tsuda ◽  
Chika Ishikawa ◽  
Hiroe Konishi ◽  
Yoshiaki Hayashi ◽  
Noboru Nakagawa ◽  
...  

ABSTRACT The production of interleukin-8 induced by the activation of protease-activated receptor 2 and its synergism with interleukin-1β were modulated by 14-membered-ring macrolides, namely, roxithromycin, erythromycin, and clarithromycin, in cultured normal human epidermal keratinocytes. Those macrolides may attenuate the protease-activated receptor 2-interleukin-8 axis and thereby modulate proinflammatory responses in the skin.

2009 ◽  
Vol 53 (5) ◽  
pp. 1760-1765 ◽  
Author(s):  
Chika Ishikawa ◽  
Tatsuya Tsuda ◽  
Hiroe Konishi ◽  
Noboru Nakagawa ◽  
Kiyofumi Yamanishi

ABSTRACT In addition to their antibiotic effects, tetracyclines have anti-inflammatory action that is often beneficial in the control of inflammatory skin disorders. In this study, we examined the effects of tetracycline (TET) and two of its derivatives, doxycycline (DOX) and minocycline (MIN), on the production of interleukin-8 (IL-8) elicited by the activation of protease-activated receptor 2 (PAR2) in normal human epidermal keratinocytes (NHEK). In NHEK, the production of IL-8 stimulated by an agonist peptide of PAR2, SLIGKIV-NH2, at 100 μM was significantly reduced by TET, DOX, or MIN at 5 and 10 μM, concentrations that are noncytotoxic. The tumor necrosis factor alpha (TNF-α)-induced production of IL-8 was synergistically augmented by SLIGKIV-NH2, and that synergistic increase in the production of IL-8 was suppressed by 100 nM PAR2-specific small interfering RNA. It was also suppressed by TET, DOX, or MIN but not by the 14-membered-ring macrolide antibiotics erythromycin, roxithromycin, and clarithromycin, which also have anti-inflammatory activities, at 10 μM. These results suggest that tetracyclines attenuate the PAR2-IL-8 axis in keratinocytes and thereby effectively modulate proinflammatory responses in the skin.


1999 ◽  
Vol 255 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Sophie Janssens ◽  
Luc Bols ◽  
Marc Vandermeeren ◽  
Guy Daneels ◽  
Marcel Borgers ◽  
...  

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