Modulation by LL-37 of the responses of salivary glands to purinergic agonists.
The interaction of mice submandibular gland cells with LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), a cationic peptide with immunomodulatory properties, was investigated. LL-37 at a concentration that did not affect the integrity of the cells increased the uptake of calcium and activated a calcium-insensitive phospholipase A(2) (PLA(2)). The small release of ATP induced by LL-37 could not account for this stimulation because apyrase did not significantly block the response to LL-37. The divalent cation magnesium inhibited the response to LL-37, but this inhibition was probably nonspecific because it also inhibited the in vitro bacteriostatic effect of the peptide. The increase of calcium uptake by LL-37 was not affected by 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), a rather specific inhibitor of P2X(7) receptors in mice. LL-37 also increased [Ca(2+)](i) in cells from mice invalidated for these receptors. LL-37 had no effect on the response to carbachol. It inhibited the increase of [Ca(2+)](i) and the activation of phospholipase D by ATP. It potentiated the activation of the PLA(2) by the nucleotide. Finally, LL-37 increased the fluidity of the plasma membrane of submandibular gland cells. In conclusion, our results suggest that LL-37 is an autocrine regulator of submandibular gland cells. It does not stimulate mouse P2X(7) receptors but modulates their responses.
Pochet
Stéphanie
S
Laboratoire de Biochimie et de Biologie Cellulaire, Université libre de Bruxelles-Institut de Pharmacie C.P. 205/3, Boulevard du Triomphe, B1050 Brussels, Belgium.
Tandel
Séverine
S
Querriére
Stéphanie
S
Tre-Hardy
Marie
M
Garcia-Marcos
Mikel
M
De Lorenzi
Manuela
M
Vandenbranden
Michel
M
Marino
Aida
A
Devleeschouwer
Michel
M
Dehaye
Jean-Paul
JP
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054513:Group IV Phospholipases A2; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000378:metabolism / Q000494:pharmacology; D010741:Phospholipases A / Q000187:drug effects; D058910:Purinergic P2 Receptor Agonists; D058486:Receptors, Purinergic P2X7; D012469:Salivary Glands / Q000187:drug effects; D013363:Submandibular Gland / Q000187:drug effects*; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D002413:Cations, Divalent; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; C546469:P2rx7 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D058486:Receptors, Purinergic P2X7; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D008274:Magnesium; D002118:Calcium; D054804:Cathelicidins