Catalytic characterization and cytokine mediated regulation of cytochrome P450 4Fs in rat hepatocytes

Auinash Kalsotra; Sayeepriyadarshini Anakk; Chad L. Brommer; Yasushi Kikuta; Edward T. Morgan; Henry W. Strobel

doi:10.1016/j.abb.2007.02.027

Catalytic characterization and cytokine mediated regulation of cytochrome P450 4Fs in rat hepatocytes

Auinash Kalsotra, Sayeepriyadarshini Anakk, Chad L. Brommer, Yasushi Kikuta, Edward T. Morgan, Henry W. Strobel

Research output: Contribution to journal › Article › peer-review

Abstract

Cytochrome P450 (CYP) 4F mediated leukotriene B₄ (LTB₄) metabolism modulates inflammation during injury and infection. Here we show that in addition to LTB₄, the recombinant rat CYP4Fs catalyze ω-hydroxylations of lipoxin A₄, and hydroxyeicosatetraeonic acids. CYP4F gene regulation studies in primary hepatocytes reveal that pro-inflammatory cytokines interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α produce a general inductive response whereas IL-10, an anti-inflammatory cytokine, suppresses CYP4F expression. The molecular mechanism behind IL-6 related induction of CYP4F4 and 4F5 is partially signal transducer and activator of transcription 3 (STAT3) dependent. When hepatocytes are subjected to high concentrations of LTB₄ or prostaglandin E₂, lipid mediators of inflammation, only an increase in CYP4F5 mRNA expression is observed. Collectively, the results from isozyme activity and substrate driven CYP4F induction do not support the notion that an autoregulatory pathway could control the excessive concentrations of LTB₄ during an inflammatory challenge to hepatocytes.

Original language	English (US)
Pages (from-to)	104-112
Number of pages	9
Journal	Archives of Biochemistry and Biophysics
Volume	461
Issue number	1
DOIs	https://doi.org/10.1016/j.abb.2007.02.027
State	Published - May 1 2007
Externally published	Yes

Keywords

Cytochrome P450 4F
Cytokines
Eicosanoids
Inflammation
Interleukin-6
Leukotriene B
STAT3

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

Online availability

10.1016/j.abb.2007.02.027

Library availability

Discover UIUC Full Text

Cite this

@article{bdba33e8814446c3ac89dec5ba9388a0,

title = "Catalytic characterization and cytokine mediated regulation of cytochrome P450 4Fs in rat hepatocytes",

abstract = "Cytochrome P450 (CYP) 4F mediated leukotriene B4 (LTB4) metabolism modulates inflammation during injury and infection. Here we show that in addition to LTB4, the recombinant rat CYP4Fs catalyze ω-hydroxylations of lipoxin A4, and hydroxyeicosatetraeonic acids. CYP4F gene regulation studies in primary hepatocytes reveal that pro-inflammatory cytokines interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α produce a general inductive response whereas IL-10, an anti-inflammatory cytokine, suppresses CYP4F expression. The molecular mechanism behind IL-6 related induction of CYP4F4 and 4F5 is partially signal transducer and activator of transcription 3 (STAT3) dependent. When hepatocytes are subjected to high concentrations of LTB4 or prostaglandin E2, lipid mediators of inflammation, only an increase in CYP4F5 mRNA expression is observed. Collectively, the results from isozyme activity and substrate driven CYP4F induction do not support the notion that an autoregulatory pathway could control the excessive concentrations of LTB4 during an inflammatory challenge to hepatocytes.",

keywords = "Cytochrome P450 4F, Cytokines, Eicosanoids, Inflammation, Interleukin-6, Leukotriene B, STAT3",

author = "Auinash Kalsotra and Sayeepriyadarshini Anakk and Brommer, {Chad L.} and Yasushi Kikuta and Morgan, {Edward T.} and Strobel, {Henry W.}",

note = "Funding Information: This work was supported by Grants R01 MH070054 and RO1 NS044174 from NIH and US Department of the Army Grant T5 0004268 for Texas Training and Technology against Trauma and Terrorism to Dr. Henry W. Strobel Grant GM 46897 to Dr. Edward T. Morgan and Medical School Dean{\textquoteright}s Research Scholarship awarded to Dr. Auinash Kalsotra. ",

year = "2007",

month = may,

day = "1",

doi = "10.1016/j.abb.2007.02.027",

language = "English (US)",

volume = "461",

pages = "104--112",

journal = "Archives of Biochemistry and Biophysics",

issn = "0003-9861",

publisher = "Academic Press Inc.",

number = "1",

}

TY - JOUR

T1 - Catalytic characterization and cytokine mediated regulation of cytochrome P450 4Fs in rat hepatocytes

AU - Kalsotra, Auinash

AU - Anakk, Sayeepriyadarshini

AU - Brommer, Chad L.

AU - Kikuta, Yasushi

AU - Morgan, Edward T.

AU - Strobel, Henry W.

N1 - Funding Information: This work was supported by Grants R01 MH070054 and RO1 NS044174 from NIH and US Department of the Army Grant T5 0004268 for Texas Training and Technology against Trauma and Terrorism to Dr. Henry W. Strobel Grant GM 46897 to Dr. Edward T. Morgan and Medical School Dean’s Research Scholarship awarded to Dr. Auinash Kalsotra.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - Cytochrome P450 (CYP) 4F mediated leukotriene B4 (LTB4) metabolism modulates inflammation during injury and infection. Here we show that in addition to LTB4, the recombinant rat CYP4Fs catalyze ω-hydroxylations of lipoxin A4, and hydroxyeicosatetraeonic acids. CYP4F gene regulation studies in primary hepatocytes reveal that pro-inflammatory cytokines interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α produce a general inductive response whereas IL-10, an anti-inflammatory cytokine, suppresses CYP4F expression. The molecular mechanism behind IL-6 related induction of CYP4F4 and 4F5 is partially signal transducer and activator of transcription 3 (STAT3) dependent. When hepatocytes are subjected to high concentrations of LTB4 or prostaglandin E2, lipid mediators of inflammation, only an increase in CYP4F5 mRNA expression is observed. Collectively, the results from isozyme activity and substrate driven CYP4F induction do not support the notion that an autoregulatory pathway could control the excessive concentrations of LTB4 during an inflammatory challenge to hepatocytes.

AB - Cytochrome P450 (CYP) 4F mediated leukotriene B4 (LTB4) metabolism modulates inflammation during injury and infection. Here we show that in addition to LTB4, the recombinant rat CYP4Fs catalyze ω-hydroxylations of lipoxin A4, and hydroxyeicosatetraeonic acids. CYP4F gene regulation studies in primary hepatocytes reveal that pro-inflammatory cytokines interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α produce a general inductive response whereas IL-10, an anti-inflammatory cytokine, suppresses CYP4F expression. The molecular mechanism behind IL-6 related induction of CYP4F4 and 4F5 is partially signal transducer and activator of transcription 3 (STAT3) dependent. When hepatocytes are subjected to high concentrations of LTB4 or prostaglandin E2, lipid mediators of inflammation, only an increase in CYP4F5 mRNA expression is observed. Collectively, the results from isozyme activity and substrate driven CYP4F induction do not support the notion that an autoregulatory pathway could control the excessive concentrations of LTB4 during an inflammatory challenge to hepatocytes.

KW - Cytochrome P450 4F

KW - Cytokines

KW - Eicosanoids

KW - Inflammation

KW - Interleukin-6

KW - Leukotriene B

KW - STAT3

UR - http://www.scopus.com/inward/record.url?scp=34247255399&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247255399&partnerID=8YFLogxK

U2 - 10.1016/j.abb.2007.02.027

DO - 10.1016/j.abb.2007.02.027

M3 - Article

C2 - 17418803

AN - SCOPUS:34247255399

SN - 0003-9861

VL - 461

SP - 104

EP - 112

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

IS - 1

ER -

Catalytic characterization and cytokine mediated regulation of cytochrome P450 4Fs in rat hepatocytes

Abstract

Keywords

ASJC Scopus subject areas

Online availability

Library availability

Related links

Fingerprint

Cite this