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Rab GTPase Mediating Regulation of NALP3 in Colorectal Cancer.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2020 Oct 20; Vol. 25 (20). Date of Electronic Publication: 2020 Oct 20. - Publication Year :
- 2020
-
Abstract
- The NALP3 inflammasome signaling contributes to inflammation within tumor tissues. This inflammation may be promoted by the vesicle trafficking of inflammasome components and cytokines. Rab5, Rab7 and Rab11 regulate vesicle trafficking. However, the role of these proteins in the regulation of inflammasomes remains largely unknown. To elucidate the role of these Rab proteins in inflammasome regulation, HCT-116, a colorectal cancer (CRC) cell line expressing pDsRed-Rab5 wild type (WT), pDsRed-Rab5 dominant-negative (DN), pDsRed-Rab7 WT, pDsRed-Rab7 DN, pDsRed-Rab11 WT and pDsRed-Rab11 DN were treated with lipopolysaccharide (LPS)/nigericin. Inflammasome activation was analyzed by measuring the mRNA expression of NLRP3 , Pro-CASP1 , RAB39A and Pro-IL-1β , conducting immunofluorescence imaging and western blotting of caspase-1 and analysing the secretion levels of IL-1β using enzyme-linked immunosorbent assay (ELISA). The effects of Rabs on cytokine release were evaluated using MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel-Premixed 41 Plex. The findings showed that LPS/nigericin-treated cells expressing Rab5-WT indicated increased NALP3 expression and secretion of the IL-1β as compared to Rab5-DN cells. Caspase-1 was localized in the nucleus and cytosol of Rab5-WT cells but was localized in the cytosol in Rab5-DN cells. There were no any effects of Rab7 and Rab11 expression on the regulation of inflammasomes. Our results suggest that Rab5 may be a potential target for the regulation of NALP3 in the treatment of the CRC inflammation.
- Subjects :
- Caspase 1 genetics
Colorectal Neoplasms pathology
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Inflammasomes genetics
Inflammation genetics
Inflammation pathology
Interleukin-1beta genetics
Signal Transduction genetics
rab7 GTP-Binding Proteins
Colorectal Neoplasms genetics
NLR Family, Pyrin Domain-Containing 3 Protein genetics
rab GTP-Binding Proteins genetics
rab5 GTP-Binding Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 25
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 33092247
- Full Text :
- https://doi.org/10.3390/molecules25204834