NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation
Nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain containing 3 (NLRP3) has recently emerged as a central regulator of innate immunity and inflammation in response to both sterile inflammatory and microbial invasion signals. Although its ability to drive proteolytic pr...
| Main Authors: | , , , |
|---|---|
| Format: | Online |
| Language: | English |
| Published: |
Public Library of Science
2015
|
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356585/ |
| id |
pubmed-4356585 |
|---|---|
| recordtype |
oai_dc |
| spelling |
pubmed-43565852015-03-17 NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation Kinoshita, Takeshi Imamura, Ryu Kushiyama, Hiroko Suda, Takashi Research Article Nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain containing 3 (NLRP3) has recently emerged as a central regulator of innate immunity and inflammation in response to both sterile inflammatory and microbial invasion signals. Although its ability to drive proteolytic procaspase-1 processing has drawn more attention, NLPR3 can also activate NF-κB. To clarify the physiological relevance of this latter function, we examined the effect of NLRP3 on NF-κB activation and cytokine induction in RNA-interference-based NLRP3-knockdown cell lines generated from the human monocytic cell line THP-1. Knocking down NLRP3 reduced NF-κB activation and cytokine induction in the early stages of Staphylococcus aureus infection. Expression of cytokine genes induced by Staphylococcus aureus was not inhibited by a caspase-1 inhibitor, and did not occur through an autocrine mechanism in response to newly synthesized cytokines. We also demonstrated that NLRP3 could activate NF-κB and induce cytokines in response to sterile signals, monosodium urate crystals and aluminum adjuvant. Thus, NLRP3 mediates NF-κB activation in both sterile and microbially induced inflammation. Our findings show that not only does NLRP3 activate caspase-1 post-translationally, but it also induces multiple cytokine genes in the innate immune system. Public Library of Science 2015-03-11 /pmc/articles/PMC4356585/ /pubmed/25761061 http://dx.doi.org/10.1371/journal.pone.0119179 Text en © 2015 Kinoshita et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kinoshita, Takeshi Imamura, Ryu Kushiyama, Hiroko Suda, Takashi |
| spellingShingle |
Kinoshita, Takeshi Imamura, Ryu Kushiyama, Hiroko Suda, Takashi NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation |
| author_facet |
Kinoshita, Takeshi Imamura, Ryu Kushiyama, Hiroko Suda, Takashi |
| author_sort |
Kinoshita, Takeshi |
| title |
NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation |
| title_short |
NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation |
| title_full |
NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation |
| title_fullStr |
NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation |
| title_full_unstemmed |
NLRP3 Mediates NF-κB Activation and Cytokine Induction in Microbially Induced and Sterile Inflammation |
| title_sort |
nlrp3 mediates nf-κb activation and cytokine induction in microbially induced and sterile inflammation |
| description |
Nucleotide-binding domain and leucine-rich repeat-containing family, pyrin domain containing 3 (NLRP3) has recently emerged as a central regulator of innate immunity and inflammation in response to both sterile inflammatory and microbial invasion signals. Although its ability to drive proteolytic procaspase-1 processing has drawn more attention, NLPR3 can also activate NF-κB. To clarify the physiological relevance of this latter function, we examined the effect of NLRP3 on NF-κB activation and cytokine induction in RNA-interference-based NLRP3-knockdown cell lines generated from the human monocytic cell line THP-1. Knocking down NLRP3 reduced NF-κB activation and cytokine induction in the early stages of Staphylococcus aureus infection. Expression of cytokine genes induced by Staphylococcus aureus was not inhibited by a caspase-1 inhibitor, and did not occur through an autocrine mechanism in response to newly synthesized cytokines. We also demonstrated that NLRP3 could activate NF-κB and induce cytokines in response to sterile signals, monosodium urate crystals and aluminum adjuvant. Thus, NLRP3 mediates NF-κB activation in both sterile and microbially induced inflammation. Our findings show that not only does NLRP3 activate caspase-1 post-translationally, but it also induces multiple cytokine genes in the innate immune system. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356585/ |
| _version_ |
1613197624857329664 |