PMID- 36681128
OWN - NLM
STAT- MEDLINE
DCOM- 20230228
LR  - 20240302
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 462
DP  - 2023 Mar 1
TI  - Scavenger receptor BI attenuates oxidized phospholipid-induced pulmonary 
      inflammation.
PG  - 116381
LID - S0041-008X(23)00019-4 [pii]
LID - 10.1016/j.taap.2023.116381 [doi]
AB  - Damage associated molecular patterns (DAMPs) are molecules released from 
      dead/dying cells following toxicant and/or environmental exposures that activate 
      the immune response through binding of pattern recognition receptors (PRRs). 
      Excessive production of DAMPs or failed clearance leads to chronic inflammation 
      and delayed inflammation resolution. One category of DAMPs are oxidized 
      phospholipids (oxPLs) produced upon exposure to high levels of oxidative stress, 
      such as following ozone (O(3)) induced inflammation. OxPLs are bound by multiple 
      classes of PRRs that include scavenger receptors (SRs) such as SR class B-1 
      (SR-BI) and toll-like receptors (TLRs). Interactions between oxPLs and PRRs 
      appear to regulate inflammation; however, the role of SR-BI in oxPL-induced lung 
      inflammation has not been defined. Therefore, we hypothesize that SR-BI is 
      critical in protecting the lung from oxPL-induced pulmonary inflammation/injury. 
      To test this hypothesis, C57BL/6J (WT) female mice were dosed with oxidized 
      1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine (oxPAPC) by 
      oropharyngeal aspiration which increased pulmonary SR-BI expression. Following 
      oxPAPC exposure, SR-BI deficient (SR-BI(-/-)) mice exhibited increased lung 
      pathology and inflammatory cytokine/chemokine production. Lipidomic analysis 
      revealed that SR-BI(-/-) mice had an altered pulmonary lipidome prior to and 
      following oxPAPC exposure, which correlated with increased oxidized 
      phosphatidylcholines (PCs). Finally, we characterized TLR4-mediated activation of 
      NF-kappaB following oxPAPC exposure and discovered that SR-BI(-/-) mice had increased 
      TLR4 mRNA expression in lung tissue and macrophages, increased nuclear p65, and 
      decreased cytoplasmic IkappaBalpha. Overall, we conclude that SR-BI is required for 
      limiting oxPAPC-induced lung pathology by maintaining lipid homeostasis, reducing 
      oxidized PCs, and attenuating TLR4-NF-kappaB activation, thereby preventing excessive 
      and persistent inflammation.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Dunigan-Russell, Katelyn
AU  - Dunigan-Russell K
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States.
FAU - Yaeger, Michael J
AU  - Yaeger MJ
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States.
FAU - Hodge, Myles X
AU  - Hodge MX
AD  - Department of Pharmacology and Toxicology, East Carolina University, Greenville, 
      NC, United States.
FAU - Kilburg-Basnyat, Brita
AU  - Kilburg-Basnyat B
AD  - Department of Pharmacology and Toxicology, East Carolina University, Greenville, 
      NC, United States.
FAU - Reece, Sky W
AU  - Reece SW
AD  - Department of Pharmacology and Toxicology, East Carolina University, Greenville, 
      NC, United States.
FAU - Birukova, Anastasiya
AU  - Birukova A
AD  - Department of Medicine, Duke University Medical Center, Durham, NC, United 
      States.
FAU - Guttenberg, Marissa A
AU  - Guttenberg MA
AD  - Department of Medicine, Duke University Medical Center, Durham, NC, United 
      States.
FAU - Novak, Caymen
AU  - Novak C
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States.
FAU - Chung, Sangwoon
AU  - Chung S
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States.
FAU - Ehrmann, Brandie Michelle
AU  - Ehrmann BM
AD  - Deparment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
FAU - Wallace, E Diane
AU  - Wallace ED
AD  - Deparment of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, 
      NC, United States.
FAU - Tokarz, Debra
AU  - Tokarz D
AD  - Experimental Pathology Laboratories, Inc., Research Triangle Park, NC, United 
      States.
FAU - Majumder, Nairrita
AU  - Majumder N
AD  - Department of Physiology and Pharmacology, West Virginia University, Morgantown, 
      WV, United States.
FAU - Xia, Li
AU  - Xia L
AD  - College of Human and Health Sciences, Purdue University, West Lafayette, IN, 
      United States.
FAU - Christman, John W
AU  - Christman JW
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States.
FAU - Shannahan, Jonathan
AU  - Shannahan J
AD  - College of Human and Health Sciences, Purdue University, West Lafayette, IN, 
      United States.
FAU - Ballinger, Megan N
AU  - Ballinger MN
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States.
FAU - Hussain, Salik
AU  - Hussain S
AD  - Department of Physiology and Pharmacology, West Virginia University, Morgantown, 
      WV, United States.
FAU - Shaikh, Saame Raza
AU  - Shaikh SR
AD  - Department of Nutrition, Gillings School of Global Public Health and School of 
      Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United 
      States.
FAU - Tighe, Robert M
AU  - Tighe RM
AD  - Department of Medicine, Duke University Medical Center, Durham, NC, United 
      States.
FAU - Gowdy, Kymberly M
AU  - Gowdy KM
AD  - Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner 
      Medical Center, Columbus, OH, United States. Electronic address: 
      kymberly.gowdy@osumc.edu.
LA  - eng
GR  - P30 ES025128/ES/NIEHS NIH HHS/United States
GR  - R01 ES027574/ES/NIEHS NIH HHS/United States
GR  - R01 ES031253/ES/NIEHS NIH HHS/United States
GR  - P30 CA016058/CA/NCI NIH HHS/United States
GR  - R01 ES028829/ES/NIEHS NIH HHS/United States
GR  - T32 ES021432/ES/NIEHS NIH HHS/United States
GR  - R01 HL137224/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230119
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Carrier Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Phospholipids)
RN  - 0 (Receptors, Scavenger)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Cd36 protein, mouse)
SB  - IM
MH  - Animals
MH  - Female
MH  - Mice
MH  - Carrier Proteins
MH  - Inflammation/chemically induced
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - *Phospholipids
MH  - *Pneumonia/chemically induced/prevention & control
MH  - Receptors, Scavenger/genetics/metabolism
MH  - Toll-Like Receptor 4/metabolism
PMC - PMC9983330
MID - NIHMS1874811
OTO - NOTNLM
OT  - DAMP
OT  - Inflammation
OT  - Lung
OT  - SR-BI
OT  - TLR4
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/01/22 06:00
MHDA- 2023/03/03 06:00
PMCR- 2024/03/01
CRDT- 2023/01/21 19:23
PHST- 2022/10/15 00:00 [received]
PHST- 2022/12/30 00:00 [revised]
PHST- 2023/01/11 00:00 [accepted]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/01/21 19:23 [entrez]
PHST- 2024/03/01 00:00 [pmc-release]
AID - S0041-008X(23)00019-4 [pii]
AID - 10.1016/j.taap.2023.116381 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2023 Mar 1;462:116381. doi: 10.1016/j.taap.2023.116381. 
      Epub 2023 Jan 19.