IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation

IL-6 was found to be overexpressed in the adipose tissue of obese individuals, which may cause insulin resistance. However, the regulation of IL-6 in adipocytes in obesity setting remains to be explored. Since IL-1β and TNFα are increased in obese adipose tissue and promote inflammation, we investig...

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Autores principales:	Areej Al-Roub, Ashraf Al Madhoun, Nadeem Akhter, Reeby Thomas, Lavina Miranda, Texy Jacob, Ebaa Al-Ozairi, Fahd Al-Mulla, Sardar Sindhu, Rasheed Ahmad
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	interleukin-1β (IL-1β) tumor necrosis factor-alpha (TNFα) adipocytes interleukin-6 (IL-6) H3K14 acetylation Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9d0b7e429f4746c09cc2ffad7865094b
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spelling	oai:doaj.org-article:9d0b7e429f4746c09cc2ffad7865094b2021-11-25T17:13:05ZIL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation10.3390/cells101132282073-4409https://doaj.org/article/9d0b7e429f4746c09cc2ffad7865094b2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3228https://doaj.org/toc/2073-4409IL-6 was found to be overexpressed in the adipose tissue of obese individuals, which may cause insulin resistance. However, the regulation of IL-6 in adipocytes in obesity setting remains to be explored. Since IL-1β and TNFα are increased in obese adipose tissue and promote inflammation, we investigated whether cooperation between IL-1β and TNFα influences the production of IL-6. Our data show that IL-1β and TNFα cooperatively enhance IL-6 expression in 3T3L-1 adipocytes. Similar results were seen in human adipocytes isolated from subcutaneous and visceral fat. Although adipocytes isolated from lean and obese adipose tissues showed similar responses for production of IL-6 when incubated with IL-1β/TNFα, secretion of IL-6 was higher in adipocytes from obese tissue. TNFα treatment enhanced CREB binding at CRE locus, which was further enhanced with IL-1β, and was associated with elevated histone acetylation at CRE locus. On the other hand, IL-1β treatments mediated C/EBPβ binding to NF-IL-6 consensus, but not sufficiently to mediate significant histone acetylation. Interestingly, treatment with both stimulatory factors amplifies CREB binding and H3K14 acetylation. Furthermore, histone acetylation inhibition by anacardic acid or curcumin reduces IL-6 production. Notably, inhibition of histone deacetylase (HDAC) activity by trichostatin A (TSA) resulted in the further elevation of IL-6 expression in response to combined treatment of adipocytes with IL-1β and TNFα. In conclusion, our results show that there is an additive interaction between IL-1β and TNFα that depends on CREB binding and H3K14 acetylation, and leads to the elevation of IL-6 expression in adipocytes, providing interesting pathophysiological connection among IL-1β, TNFα, and IL-6 in settings such as obesity.Areej Al-RoubAshraf Al MadhounNadeem AkhterReeby ThomasLavina MirandaTexy JacobEbaa Al-OzairiFahd Al-MullaSardar SindhuRasheed AhmadMDPI AGarticleinterleukin-1β (IL-1β)tumor necrosis factor-alpha (TNFα)adipocytesinterleukin-6 (IL-6)H3K14 acetylationBiology (General)QH301-705.5ENCells, Vol 10, Iss 3228, p 3228 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	interleukin-1β (IL-1β) tumor necrosis factor-alpha (TNFα) adipocytes interleukin-6 (IL-6) H3K14 acetylation Biology (General) QH301-705.5
spellingShingle	interleukin-1β (IL-1β) tumor necrosis factor-alpha (TNFα) adipocytes interleukin-6 (IL-6) H3K14 acetylation Biology (General) QH301-705.5 Areej Al-Roub Ashraf Al Madhoun Nadeem Akhter Reeby Thomas Lavina Miranda Texy Jacob Ebaa Al-Ozairi Fahd Al-Mulla Sardar Sindhu Rasheed Ahmad IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation
description	IL-6 was found to be overexpressed in the adipose tissue of obese individuals, which may cause insulin resistance. However, the regulation of IL-6 in adipocytes in obesity setting remains to be explored. Since IL-1β and TNFα are increased in obese adipose tissue and promote inflammation, we investigated whether cooperation between IL-1β and TNFα influences the production of IL-6. Our data show that IL-1β and TNFα cooperatively enhance IL-6 expression in 3T3L-1 adipocytes. Similar results were seen in human adipocytes isolated from subcutaneous and visceral fat. Although adipocytes isolated from lean and obese adipose tissues showed similar responses for production of IL-6 when incubated with IL-1β/TNFα, secretion of IL-6 was higher in adipocytes from obese tissue. TNFα treatment enhanced CREB binding at CRE locus, which was further enhanced with IL-1β, and was associated with elevated histone acetylation at CRE locus. On the other hand, IL-1β treatments mediated C/EBPβ binding to NF-IL-6 consensus, but not sufficiently to mediate significant histone acetylation. Interestingly, treatment with both stimulatory factors amplifies CREB binding and H3K14 acetylation. Furthermore, histone acetylation inhibition by anacardic acid or curcumin reduces IL-6 production. Notably, inhibition of histone deacetylase (HDAC) activity by trichostatin A (TSA) resulted in the further elevation of IL-6 expression in response to combined treatment of adipocytes with IL-1β and TNFα. In conclusion, our results show that there is an additive interaction between IL-1β and TNFα that depends on CREB binding and H3K14 acetylation, and leads to the elevation of IL-6 expression in adipocytes, providing interesting pathophysiological connection among IL-1β, TNFα, and IL-6 in settings such as obesity.
format	article
author	Areej Al-Roub Ashraf Al Madhoun Nadeem Akhter Reeby Thomas Lavina Miranda Texy Jacob Ebaa Al-Ozairi Fahd Al-Mulla Sardar Sindhu Rasheed Ahmad
author_facet	Areej Al-Roub Ashraf Al Madhoun Nadeem Akhter Reeby Thomas Lavina Miranda Texy Jacob Ebaa Al-Ozairi Fahd Al-Mulla Sardar Sindhu Rasheed Ahmad
author_sort	Areej Al-Roub
title	IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation
title_short	IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation
title_full	IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation
title_fullStr	IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation
title_full_unstemmed	IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation
title_sort	il-1β and tnfα cooperativity in regulating il-6 expression in adipocytes depends on creb binding and h3k14 acetylation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9d0b7e429f4746c09cc2ffad7865094b
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IL-1β and TNFα Cooperativity in Regulating IL-6 Expression in Adipocytes Depends on CREB Binding and H3K14 Acetylation

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