Inflammasome Coordinates Senescent Chronic Wound Induced by Thalassophryne nattereri Venom
Thalassophryne nattereri toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages. Macrophages and neutrophils are actively recruited to clear debris during the inflammatory phase of wound repair, promoting the production of pro-inflammatory mediators, and in the late stage, macrophages promote tissue repair. Our hypothesis is that injury caused by T. nattereri venom (VTn) leads to senescent wounds. In this study, we provide valuable information about the mechanism(s) behind the dysregulated inflammation in wound healing induced by VTn. We demonstrate in mouse paws injected with the venom the installation of γH2AX/p16Ink4a-dependent senescence with persistent neutrophilic inflammation in the proliferation and remodeling phases. VTn induced an imbalance of M1/M2 macrophages by maintaining a high number of TNF-α-producing M1 macrophages in the wound but without the ability to eliminate the persistent neutrophils. Chronic neutrophilic inflammation and senescence were mediated by cytokines such as IL-1α and IL-1β in a caspase-1- and caspase-11-dependent manner. In addition, previous blocking with anti-IL-1α and anti-IL-β neutralizing antibodies and caspase-1 (Ac YVAD-CMK) and caspase-11 (Wedelolactone) inhibitors was essential to control the pro-inflammatory activity of M1 macrophages induced by VTn injection, skewing towards an anti-inflammatory state, and was sufficient to block neutrophil recruitment and senescence.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
International journal of molecular sciences - 24(2023), 9 vom: 08. Mai |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Lima, Carla [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 15.05.2023 Date Revised 15.05.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/ijms24098453 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356789365 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356789365 | ||
| 003 | DE-627 | ||
| 005 | 20231226071218.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/ijms24098453 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1189.xml |
| 035 | |a (DE-627)NLM356789365 | ||
| 035 | |a (NLM)37176162 | ||
| 035 | |a (PII)8453 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Lima, Carla |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Inflammasome Coordinates Senescent Chronic Wound Induced by Thalassophryne nattereri Venom |
| 264 | 1 | |c 2023 | |
| 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 15.05.2023 | ||
| 500 | |a Date Revised 15.05.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Thalassophryne nattereri toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages. Macrophages and neutrophils are actively recruited to clear debris during the inflammatory phase of wound repair, promoting the production of pro-inflammatory mediators, and in the late stage, macrophages promote tissue repair. Our hypothesis is that injury caused by T. nattereri venom (VTn) leads to senescent wounds. In this study, we provide valuable information about the mechanism(s) behind the dysregulated inflammation in wound healing induced by VTn. We demonstrate in mouse paws injected with the venom the installation of γH2AX/p16Ink4a-dependent senescence with persistent neutrophilic inflammation in the proliferation and remodeling phases. VTn induced an imbalance of M1/M2 macrophages by maintaining a high number of TNF-α-producing M1 macrophages in the wound but without the ability to eliminate the persistent neutrophils. Chronic neutrophilic inflammation and senescence were mediated by cytokines such as IL-1α and IL-1β in a caspase-1- and caspase-11-dependent manner. In addition, previous blocking with anti-IL-1α and anti-IL-β neutralizing antibodies and caspase-1 (Ac YVAD-CMK) and caspase-11 (Wedelolactone) inhibitors was essential to control the pro-inflammatory activity of M1 macrophages induced by VTn injection, skewing towards an anti-inflammatory state, and was sufficient to block neutrophil recruitment and senescence | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IL-1α/β | |
| 650 | 4 | |a M1/M2 macrophages | |
| 650 | 4 | |a Thalassophryne nattereri | |
| 650 | 4 | |a caspase-1/-11 | |
| 650 | 4 | |a inflammasome complex | |
| 650 | 4 | |a innate cells | |
| 650 | 4 | |a necrosis | |
| 650 | 4 | |a neutrophils | |
| 650 | 4 | |a repair | |
| 650 | 4 | |a senescence | |
| 650 | 4 | |a wound healing | |
| 650 | 7 | |a Venoms |2 NLM | |
| 650 | 7 | |a Fish Venoms |2 NLM | |
| 650 | 7 | |a Inflammasomes |2 NLM | |
| 650 | 7 | |a Caspase 1 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.36 |2 NLM | |
| 700 | 1 | |a Andrade-Barros, Aline Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Carvalho, Fabiana Franco |e verfasserin |4 aut | |
| 700 | 1 | |a Falcão, Maria Alice Pimentel |e verfasserin |4 aut | |
| 700 | 1 | |a Lopes-Ferreira, Monica |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 24(2023), 9 vom: 08. Mai |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:9 |g day:08 |g month:05 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms24098453 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 9 |b 08 |c 05 | ||