RGD Reference Report - Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro. - Rat Genome Database

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Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro.

Authors: Lalaker, A  Nkrumah, L  Lee, WK  Ramanathan, M  Lane, AP 
Citation: Lalaker A, etal., Am J Rhinol Allergy. 2009 Jan-Feb;23(1):8-14.
RGD ID: 5037227
Pubmed: PMID:19379605   (View Abstract at PubMed)
PMCID: PMC2904690   (View Article at PubMed Central)
DOI: DOI:10.2500/ajra.2009.23.3256   (Journal Full-text)

BACKGROUND: Sinonasal epithelial cells participate in host defense by initiating innate immune mechanisms against potential pathogens. Antimicrobial innate mechanisms have been shown to involve Th1-like inflammatory responses. Although epithelial cells can also be induced by Th2 cytokines to express proeosinophilic mediators, no environmental agents have been identified that promote this effect. METHODS: Human sinonasal epithelial cells from patients with chronic rhinosinusitis with nasal polyps (CRSwNPs) and controls were harvested and grown in primary culture. Cell cultures were exposed to a range of concentrations of chitin for 24 hours, and mRNA for acidic mammalian chitinase (AMCase), eotaxin-3, and thymic stromal-derived lymphopoietin (TSLP) were assessed. Other cultures were exposed to interleukin 4 (IL- 4) alone and in combination with dust-mite antigen (DMA) for 36 hours. Extracted mRNA and cell culture supernatant were analyzed for expression of AMCase and eotaxin-3. RESULTS: Chitin induced a dose-dependent expression of AMCase and eotaxin-3 mRNA but not TSLP. Patients with recalcitrant CRSwNPs showed lower baseline expression of AMCase when compared with treatment-responsive CRSwNP and less induction of AMCase expression by chitin. DMA did not directly induce expression of AMCase or eotaxin-3. Expression of eotaxin-3 was stimulated by IL-4 and further enhanced with the addition of DMA. Levels of AMCase were not significantly affected by either IL-4 or DMA exposure. In some cases, the combination of IL-4 and DMA was able to induce AMCase expression in cell cultures not producing AMCase at baseline. CONCLUSION: The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. This finding suggests the existence of a novel innate immune pathway for local defense against chitin-containing organisms in the sinonasal tract. Dysregulation of this function could precipitate or exacerbate Th2 inflammation, potentially acting as an underlying factor in recalcitrant CRSwNP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sinusitis severityIEP 5037227mRNA:decreased expression:sinus and epithelial cell (human)RGD 
sinusitis severityISOCHIA (Homo sapiens)5037227; 5037227mRNA:decreased expression:sinus and epithelial cell (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Chia  (chitinase, acidic)

Genes (Mus musculus)
Chia1  (chitinase, acidic 1)

Genes (Homo sapiens)
CHIA  (chitinase acidic)


Additional Information