Roles of caspase 1 and extracellular signal-regulated kinase in inflammation-induced inhibition of lacrimal gland protein secretion.

Abstract

PURPOSE:

The purpose of the present study was to investigate the roles of caspase 1 and extracellular signal-regulated kinase (ERK) in inflammation-induced inhibition of lacrimal gland secretion.

METHODS:

Lacrimal gland inflammation was induced by injection of lipopolysaccharide (LPS; to study the role of caspase 1) or IL-1beta (to study the role of ERK). Lacrimal gland protein secretion was measured using a spectrofluorometric assay. Caspase 1 and ERK activities in the lacrimal gland were measured by immunohistochemistry, Western blotting, or both. Aqueous tear production was measured using phenol red-impregnated cotton threads.

RESULTS:

Injection of LPS into the lacrimal gland inhibited neurally and adrenergic agonist-induced protein secretion by 77% and 54%, respectively, and activated caspase 1. The degree of inhibition achieved by LPS was similar to that obtained with injection of IL-1beta. Inhibition of caspase 1 alleviated the inhibitory effect of LPS on lacrimal gland secretion. IL-1beta activated ERK in the lacrimal gland in vitro and in vivo, and this effect was blocked by UO126, an inhibitor of MEK, the ERK-activating enzyme. IL-1beta injection into the lacrimal gland inhibited aqueous tear production by 52% and inhibited neurally and adrenergic agonist-induced protein secretion by 80% and 55%, respectively. UO126 alleviated the inhibitory effect of IL-1beta on aqueous tear production and lacrimal gland protein secretion.

CONCLUSIONS:

LPS inhibits lacrimal gland secretion by activating caspase 1, and IL-1beta activates the ERK pathway to inhibit lacrimal gland protein secretion and aqueous tear production.

• Authors: Driss Zoukhri, Sunghwan Ko, Paul C Stark, Claire L Kublin
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 49 Issue 10 Pg. 4392-8 (Oct 2008) ISSN: 1552-5783 [Electronic] United States
• PMID: 18566460 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Butadienes
• Enzyme Inhibitors
• Eye Proteins
• Interleukin-1beta
• Lipopolysaccharides
• Nitriles
• Recombinant Proteins
• U 0126
• tear proteins
• Extracellular Signal-Regulated MAP Kinases
• Caspase 1

Topics

• Animals
• Blotting, Western
• Butadienes (pharmacology)
• Caspase 1 (metabolism)
• Dacryocystitis (chemically induced, enzymology)
• Enzyme Activation
• Enzyme Inhibitors (pharmacology)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Eye Proteins (metabolism)
• Female
• Fluorescent Antibody Technique, Indirect
• Inflammation (chemically induced, enzymology)
• Interleukin-1beta (pharmacology)
• Lacrimal Apparatus (drug effects, enzymology)
• Lipopolysaccharides
• Mice
• Mice, Inbred BALB C
• Nitriles (pharmacology)
• Recombinant Proteins (pharmacology)
• Spectrometry, Fluorescence
• Tears (metabolism)