Increased expression of cathepsins and obesity-induced proinflammatory cytokines in lacrimal glands of male NOD mouse.
OBJECTIVE
Lacrimal glands (LGs) of male NOD mice, a model of Sjögren's syndrome (SjS), exhibit immune cell infiltration and lipid deposition. The mechanism of SjS was further investigated by characterizing gene expression profiles of NOD mouse LGs in comparison with those of healthy control mice. Differentially expressed genes were further investigated at the protein level to correlate changes in location and abundance with development of disease.


METHODS
Microarray followed by real-time RT-PCR was conducted to compare the gene expression in 12-week-old male NOD mouse LG relative to that in matched BALB/c mouse LG. Immunofluorescence and Western blot analyses were used to localize and quantify proteins of interest. Enzymatic assays measured catalytic activity of cathepsins.


RESULTS
Cathepsin H (Ctsh), S (Ctss), and Z (Ctsz) and proinflammatory factors, including tumor necrosis factor (Tnf), interleukin 6 (Il6), and interleukin 1 beta (Il1b), were upregulated at the mRNA level. Increased cathepsin S immunofluorescence was detected in lysosomes and secretory vesicle-like organelles in LG acinar cells and CD68-positive infiltrating macrophages in NOD mouse LG. Cathepsin S (CATS) and cathepsin H (CATH) activities were significantly higher in NOD mouse LG lysate than in control lysates, and CATS was also significantly elevated in NOD mouse tears.


CONCLUSIONS
Expression of CATS and CATH increases in parallel with proinflammatory cytokines during the development of autoimmune inflammatory disease in the NOD mouse disease model. Tear CATS may represent a biomarker for diagnosis of dacryoadenitis in SjS.
Li
Xiaodong
X
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California, USA.
Wu
Kaijin
K
Edman
Maria
M
Schenke-Layland
Katja
K
MacVeigh-Aloni
Michelle
M
Janga
Srikanth Reddy
SR
Schulz
Barbara
B
Hamm-Alvarez
Sarah F
SF
D000818:Animals; D015153:Blotting, Western; D002403:Cathepsins / Q000235:genetics* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D003607:Dacryocystitis / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology*; D007765:Lacrimal Apparatus / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013666:Tears / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D002403:Cathepsins
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