PMID- 35837195
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2078-6891 (Print)
IS  - 2219-679X (Electronic)
IS  - 2078-6891 (Linking)
VI  - 13
IP  - 3
DP  - 2022 Jun
TI  - IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 
      inflammasome by tumor-associated macrophages in hepatocellular carcinoma.
PG  - 1317-1329
LID - 10.21037/jgo-22-471 [doi]
AB  - BACKGROUND: Hepatocellular carcinomas (HCCs) occur frequently in the digestive 
      system and are associated with high mortality. This current study examined the 
      regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 
      (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and 
      tumor-associated macrophages (TAMs) in the growth and metastasis of HCC. METHODS: 
      The expression of IRAK1 and NLRP3 was assessed in tissues and cells via 
      quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot 
      analysis. Immunohistology was performed to detect the macrophage markers CD68, 
      CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 
      (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 
      transfection and/or co-culture with TAMs, HCC cell viability, proliferation, 
      migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory 
      cytokines IL-1 beta, IL-18, and monocyte chemotactic protein 1 (MCP-1) were 
      assessed. RESULTS: HCC tissues showed elevated expression of IRAK1 and NLRP3, as 
      well as increased expression of the macrophage markers CD68, CD163, and CD168, 
      compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and 
      Huh7 cells resulted in suppression of cell proliferation, migration, and 
      invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines 
      IL-1beta, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell 
      proliferation, migration, and invasion, and elevated the expression of NLRP3, 
      IL-1beta, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of 
      TAMs on HepG2 and Huh7 cells. CONCLUSIONS: The expression of IRAK1 was associated 
      with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The 
      ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 
      inflammasomes and regulated by IRAK1.
CI  - 2022 Journal of Gastrointestinal Oncology. All rights reserved.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Oncology, People's Hospital of Huadu District, Guangzhou, China.
FAU - Hu, Mingjuan
AU  - Hu M
AD  - Department of Pathology, People's Hospital of Huadu District, Guangzhou, China.
FAU - Wei, Tao
AU  - Wei T
AD  - Department of Oncology, People's Hospital of Huadu District, Guangzhou, China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Department of Oncology, People's Hospital of Huadu District, Guangzhou, China.
FAU - Tan, Tian
AU  - Tan T
AD  - Department of Oncology, People's Hospital of Huadu District, Guangzhou, China.
FAU - Zhang, Chengfang
AU  - Zhang C
AD  - Department of Oncology, People's Hospital of Huadu District, Guangzhou, China.
FAU - Weng, Jiaxuan
AU  - Weng J
AD  - Department of Oncology, People's Hospital of Huadu District, Guangzhou, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - J Gastrointest Oncol
JT  - Journal of gastrointestinal oncology
JID - 101557751
PMC - PMC9274051
OTO - NOTNLM
OT  - Hepatocellular carcinoma (HCC)
OT  - IL-1 receptor-associated kinase 1 (IRAK1)
OT  - NLR family pyrin domain-containing 3 (NLRP3)
OT  - inflammation
OT  - tumor-associated macrophages (TAMs)
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at 
      https://jgo.amegroups.com/article/view/10.21037/jgo-22-471/coif). The authors 
      have no conflicts of interest to declare.
EDAT- 2022/07/16 06:00
MHDA- 2022/07/16 06:01
PMCR- 2022/06/01
CRDT- 2022/07/15 02:36
PHST- 2022/04/14 00:00 [received]
PHST- 2022/06/16 00:00 [accepted]
PHST- 2022/07/15 02:36 [entrez]
PHST- 2022/07/16 06:00 [pubmed]
PHST- 2022/07/16 06:01 [medline]
PHST- 2022/06/01 00:00 [pmc-release]
AID - jgo-13-03-1317 [pii]
AID - 10.21037/jgo-22-471 [doi]
PST - ppublish
SO  - J Gastrointest Oncol. 2022 Jun;13(3):1317-1329. doi: 10.21037/jgo-22-471.