SLPI

Antileukoproteinase precursor (ALP) (BLPI) (HUSI-1) (Mucus proteinase inhibitor) (MPI) (Protease inhibitor WAP4) (Secretory leukocyte protease inhibitor) (Seminal proteinase inhibitor) (WAP four-disulfide core domain protein 4) [WAP4] [WFDC4]

Publications

Human buccal epithelium acquires microbial hyporesponsiveness at birth, a role for secretory leukocyte protease inhibitor.

PubMed

Full text

Repetitive interaction with microbial stimuli renders epithelial cells (ECs) hyporesponsive to microbial stimulation. Previously, we have reported that buccal ECs from a subset of paediatric patients with Crohn's disease are not hyporesponsive and spontaneously released chemokines. We now aimed to identify kinetics and mechanisms of acquisition of hyporesponsiveness to microbial stimulation using primary human buccal epithelium. Buccal ECs collected directly after birth and in later stages of life were investigated. Chemokine release and regulatory signalling pathways were studied using primary buccal ECs and the buccal EC line TR146. Findings were extended to the intestinal mucosa using murine model systems. Directly after birth, primary human buccal ECs spontaneously produced the chemokine CXCL-8 and were responsive to microbial stimuli. Within the first weeks of life, these ECs attained hyporesponsiveness, associated with inactivation of the NF-κB pathway and upregulation of the novel NF-κB inhibitor SLPI but no other known NF-κB inhibitors. SLPI protein was abundant in the cytoplasm and the nucleus of hyporesponsive buccal ECs. Knock-down of SLPI in TR146-buccal ECs induced loss of hyporesponsiveness with increased NF-κB activation and subsequent chemokine release. This regulatory mechanism extended to the intestine, as colonisation of germfree mice elicited SLPI expression in small intestine and colon. Moreover, SLPI-deficient mice had increased chemokine expression in small intestinal and colonic ECs. We identify SLPI as a new player in acquisition of microbial hyporesponsiveness by buccal and intestinal epithelium in the first weeks after microbial colonisation.

MeSH Terms

• Adult
• Aging
• Animals
• Cells, Cultured
• Chemokine CXCL2
• Down-Regulation
• Epithelium
• Gene Knockdown Techniques
• Humans
• Immune Tolerance
• Infant
• Infant, Newborn
• Interleukin-8
• Intestinal Mucosa
• Mice
• Middle Aged
• Mouth Mucosa
• NF-kappa B
• Peptidoglycan
• Secretory Leukocyte Peptidase Inhibitor

Keywords

• Bacterial Interactions
• Epithelial Cells
• Gut Immunology
• IBD Basic Research