PMID- 36505497
OWN - NLM
STAT- MEDLINE
DCOM- 20230105
LR  - 20230427
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Determining distinct roles of IL-1alpha through generation of an IL-1alpha knockout mouse 
      with no defect in IL-1beta expression.
PG  - 1068230
LID - 10.3389/fimmu.2022.1068230 [doi]
LID - 1068230
AB  - Interleukin 1alpha (IL-1alpha) and IL-1beta are the founding members of the IL-1 cytokine 
      family, and these innate immune inflammatory mediators are critically important 
      in health and disease. Early studies on these molecules suggested that their 
      expression was interdependent, with an initial genetic model of IL-1alpha depletion, 
      the IL-1alpha KO mouse (Il1a-KO(line1)), showing reduced IL-1beta expression. However, 
      studies using this line in models of infection and inflammation resulted in 
      contrasting observations. To overcome the limitations of this genetic model, we 
      have generated and characterized a new line of IL-1alpha KO mice (Il1a-KO(line2)) 
      using CRISPR-Cas9 technology. In contrast to cells from Il1a-KO(line1), where 
      IL-1beta expression was drastically reduced, bone marrow-derived macrophages (BMDMs) 
      from Il1a-KO(line2) mice showed normal induction and activation of IL-1beta. 
      Additionally, Il1a-KO(line2) BMDMs showed normal inflammasome activation and 
      IL-1beta expression in response to multiple innate immune triggers, including both 
      pathogen-associated molecular patterns and pathogens. Moreover, using 
      Il1a-KO(line2) cells, we confirmed that IL-1alpha, independent of IL-1beta, is critical 
      for the expression of the neutrophil chemoattractant KC/CXCL1. Overall, we report 
      the generation of a new line of IL-1alpha KO mice and confirm functions for IL-1alpha 
      independent of IL-1beta. Future studies on the unique functions of IL-1alpha and IL-1beta 
      using these mice will be critical to identify new roles for these molecules in 
      health and disease and develop therapeutic strategies.
CI  - Copyright (c) 2022 Malireddi, Bynigeri, Kancharana, Sharma, Burton, Pelletier and 
      Kanneganti.
FAU - Malireddi, R K Subbarao
AU  - Malireddi RKS
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
FAU - Bynigeri, Ratnakar R
AU  - Bynigeri RR
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
FAU - Kancharana, Balabhaskararao
AU  - Kancharana B
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
FAU - Sharma, Bhesh Raj
AU  - Sharma BR
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
FAU - Burton, Amanda R
AU  - Burton AR
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
FAU - Pelletier, Stephane
AU  - Pelletier S
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
FAU - Kanneganti, Thirumala-Devi
AU  - Kanneganti TD
AD  - Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, 
      United States.
LA  - eng
GR  - R35 CA253095/CA/NCI NIH HHS/United States
GR  - R01 AI124346/AI/NIAID NIH HHS/United States
GR  - R37 AI101935/AI/NIAID NIH HHS/United States
GR  - R01 AI160179/AI/NIAID NIH HHS/United States
GR  - R01 AR056296/AR/NIAMS NIH HHS/United States
PT  - Journal Article
DEP - 20221124
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (Interleukin-8)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Il1a protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Inflammasomes/genetics
MH  - *Interleukin-1alpha/genetics
MH  - Interleukin-8
MH  - Macrophages
MH  - Mice, Knockout
PMC - PMC9729281
OTO - NOTNLM
OT  - CXCL1
OT  - IL-1alpha
OT  - IL-1beta
OT  - PAMP
OT  - caspase-1
OT  - inflammasome
OT  - inflammation
OT  - innate immunity
COIS- T-DK is a consultant for Pfizer. The remaining authors declare that the research 
      was conducted in the absence of any commercial or financial relationships that 
      could be construed as a potential conflict of interest.
EDAT- 2022/12/13 06:00
MHDA- 2022/12/15 06:00
PMCR- 2022/01/01
CRDT- 2022/12/12 11:01
PHST- 2022/10/12 00:00 [received]
PHST- 2022/11/10 00:00 [accepted]
PHST- 2022/12/12 11:01 [entrez]
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2022/12/15 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.1068230 [doi]
PST - epublish
SO  - Front Immunol. 2022 Nov 24;13:1068230. doi: 10.3389/fimmu.2022.1068230. 
      eCollection 2022.