Antileukoproteinase: Modulation of neutrophil function and therapeutic effects on anti–type II collagen antibody–induced arthritis

Sehnert, Bettina; Cavcic, A; Böhm, Beate; Kalden, Joachim R.; Nandakumar, Kutty Selva; Holmdahl, Rikard; Burkhardt, Harald

doi:10.1002/art.20339

Cited by 32 publications

(41 citation statements)

References 39 publications

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“…The MUC1 gene encodes mucin 1, which contributes to the buildup of the protective glycocalyx layer. The SLPI gene codes for a leukocyte protease inhibitor which, like ␣ 1 -antichymotrypsin, may prevent damage of the mucosa caused by neutrophil proteases (37). In addition, the SLPI product exerts its protective effect not only by inhibiting various proteinases secreted by the host but also by displaying antimicrobial activity and by being involved in tissue repair reactions (18).…”

Section: Resultsmentioning

confidence: 99%

Broad Up-Regulation of Innate Defense Factors during Acute Cholera

et al. 2007

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We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute-and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (␣ 1 -antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.

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Section: Resultsmentioning

confidence: 99%

Broad Up-Regulation of Innate Defense Factors during Acute Cholera

et al. 2007

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“…As an anti-inflammatory cytokine, SLPI decreased the inflammatory response in the conjunctiva with the viral antigen to suppress the infiltration and degranulation of eosinophil (33). In addition, SLPI decreased the tissue injury via the inflammatory response in arthritis as the reducing infiltration of neutrophils (34). As a protease inhibitor, SLPI protected against injuries to the human bronchial tissue through an inflammatory response by inhibiting the elastase activity secreted from neutrophils (4).…”

Section: Discussionmentioning

confidence: 99%

Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells

Choi

Jeong²,

Wang³

et al. 2011

Int J Mol Med

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Abstract. Secretory leukocyte protease inhibitor (SLPI) protects tissue from proteases, and promotes cell proliferation and healing during inflammatory response. SLPI is also overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. Matrix metalloproteinases-2, -9 (MMP-2 and MMP-9) are overexpressed in high metastatic cancers, and promote the migration of cancer cells through collagen degradation. SLPI and MMP-2, -9 are critical factors in stimulating the metastatic processes but there are no reports of a direct correlation between these molecules. Therefore, this study examined the role of SLPI related to MMP-2 and MMP-9 using two gastric cancer cell lines, such as characterized non-metastatic SNU484 and highly metastatic SNU638 cells. SLPI, MMP-2 and MMP-9 mRNA and protein expression were higher in SNU638 cells than in SNU484 cells. In addition, the rate of cell migration and invasion was higher in the SNU638 cells than in SNU484 cells. Interestingly, after treatment with SLPI, the rate of migration and invasion was higher in the SNU484 cells than in the positive control (PC) SNU484 cells. The rate of migration was also higher in the SNU638 cells after SLPI treatment than in the SNU638 cells (PC) but the invasion rate was not changed. The expression and secretion of MMP-2 and MMP-9 as well the rate of cell migration and invasion were significantly lower in SLPIsiRNA transfected SNU638 cells (si-SLPI/SNU638) but higher in SLPI-treated SNU484 cells (SNU484 + SLPI). Strong Elk-1 phosphorylation was detected in SNU484 + SLPI and SNU638 cells but was barely detectable in SNU484 and si-SLPI/SNU638 cells. These results show that SLPI promotes the metastasis of SNU638 gastric cancer cells by increasing MMP-2 and MMP-9 expression through Elk-1 signaling, indicating its role as a signaling molecule not a protease inhibitor. IntroductionThe metastatic cascade of cancer cells is viewed as a series of sequential and interrelated steps, which include the following: epithelial-mesenchymal transition (EMT), degradation of the basement membrane; dissociation of tumor cells from the primary site; invasion of the neighboring tissue; intravasation into the blood and lymph vessels; transport through the vessels; extravasation from the vessels; and proliferation at a distant site. Among these processes, tumor cells invading the neighboring tissue after degrading the basement membrane is a major development (1).Secretory leukocyte protease inhibitor (SLPI) is an 11.7-kDa cystein-rich protein and an epithelial cell product found in saliva, seminal plasma and in the cervical, nasal, and bronchial mucus. SLPI inhibits the serine protease activity, such as chymotrypsin, trypsin, pancreatic elastase, cathepsin G, mast cell chymase (2). Recently, SLPI was reported to be an anti-inflammatory factor that contributes at the early inflammatory response in odontoblasts (3). In addition, SLPI was reported to play a role not only in protecting the tissues from the protease (4) but also in promoting wou...

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“…The serine protease inhibitors antileukopeptidase and squamous cell carcinoma antigen were induced. Antileukopeptidase prevents cartilage and bone erosion in anti-type II collagen antibody-induced arthritis (40). Activin A is a member of the transforming growth factor ␤ (TGF␤) superfamily, mediating its affects through Smad transcription factors.…”

Section: Discussionmentioning

confidence: 99%