Anti-inflammation of LZTFL1 knockdown in OVA-induced asthmatic mice : Through ERK/GATA3 signaling pathway
Copyright © 2024 Elsevier Ltd. All rights reserved..
Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 107 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2024 |
---|---|
Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:167 |
---|---|
Enthalten in: |
Molecular immunology - 167(2024) vom: 27. März, Seite 16-24 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Song, Guihua [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 26.02.2024 Date Revised 29.02.2024 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.molimm.2024.01.010 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM36800175X |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM36800175X | ||
003 | DE-627 | ||
005 | 20240301232445.0 | ||
007 | cr uuu---uuuuu | ||
008 | 240205s2024 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.molimm.2024.01.010 |2 doi | |
028 | 5 | 2 | |a pubmed24n1313.xml |
035 | |a (DE-627)NLM36800175X | ||
035 | |a (NLM)38310669 | ||
035 | |a (PII)S0161-5890(24)00018-X | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Song, Guihua |e verfasserin |4 aut | |
245 | 1 | 0 | |a Anti-inflammation of LZTFL1 knockdown in OVA-induced asthmatic mice |b Through ERK/GATA3 signaling pathway |
264 | 1 | |c 2024 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 26.02.2024 | ||
500 | |a Date Revised 29.02.2024 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2024 Elsevier Ltd. All rights reserved. | ||
520 | |a Asthma is a common chronic respiratory disease characterized by Th2-type inflammation in the airways. Leucine zip transcription factor-like 1 (LZTFL1) has been implicated in the regulation of Th2-related factors. The knockdown of LZTFL1 resulted in decreased levels of IL-4, IL-5, and IL-13. We hypothesize that LZTFL1 may have an effect on asthma. We established an acute asthmatic mouse model using the Ovalbumin (OVA) sensitization, and we found that LZTFL1 expression was upregulated in OVA-induced CD4 + T cells. Mice challenged with OVA were administered 5 × 107 TU of lentivirus via tail vein injection. LZTFL1 knockdown reversed the frequency of sneezing and nose rubbing in OVA mice. LZTFL1 knockdown reduced inflammatory cell infiltration, reduced goblet cell numbers, and mitigated collagen deposition in lung tissue. LZTFL1 knockdown decreased the levels of OVA-specific IgE, IL-4, IL-5, and IL-13 in alveolar lavage fluid of asthmatic mice. Furthermore, LZTFL1 knockdown inhibited the aberrant activation of MEK/ERK signaling pathway in asthmatic mice. GATA binding protein 3 (GATA3) is an essential transcription factor in Th2 differentiation. Flow cytometry results revealed that LZTFL1 knockdown reduced the number of GATA3 + CD4 + Th2 cells, while it did not affect the stability of GATA3 mRNA. This may be attributed to ERK signaling which stabilized GATA3 by preventing its ubiquitination and subsequent degradation. In conclusion, LZTFL1 knockdown attenuates inflammation and pathological changes in OVA-induced asthmatic mice through ERK/GATA3 signaling pathway | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Asthma | |
650 | 4 | |a LZTFL1 | |
650 | 4 | |a MEK/ERK signaling | |
650 | 4 | |a Th2 inflammation | |
650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
650 | 7 | |a Cytokines |2 NLM | |
650 | 7 | |a Gata3 protein, mouse |2 NLM | |
650 | 7 | |a Interleukin-13 |2 NLM | |
650 | 7 | |a Interleukin-4 |2 NLM | |
650 | 7 | |a 207137-56-2 |2 NLM | |
650 | 7 | |a Interleukin-5 |2 NLM | |
650 | 7 | |a Lztfl1 protein, mouse |2 NLM | |
650 | 7 | |a Ovalbumin |2 NLM | |
650 | 7 | |a 9006-59-1 |2 NLM | |
650 | 7 | |a Transcription Factors |2 NLM | |
700 | 1 | |a Sun, Mengmeng |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Bingxue |e verfasserin |4 aut | |
700 | 1 | |a Peng, Minghao |e verfasserin |4 aut | |
700 | 1 | |a Bao, Beibei |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Molecular immunology |d 1984 |g 167(2024) vom: 27. März, Seite 16-24 |w (DE-627)NLM000411434 |x 1872-9142 |7 nnns |
773 | 1 | 8 | |g volume:167 |g year:2024 |g day:27 |g month:03 |g pages:16-24 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.molimm.2024.01.010 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 167 |j 2024 |b 27 |c 03 |h 16-24 |