LincRNA-Cox2 functions to regulate inflammation in alveolar macrophages during acute lung injury

Details

• Alternative Title:
  J Immunol
• Personal Author:
  Robinson, Elektra Kantzari ; Worthington, Atesh ; Poscablo, Donna ; Shapleigh, Barbara ; Salih, Mays Mohammed ; Halasz, Haley ; Seninge, Lucas ; Mosqueira, Benny ; Smaliy, Valeriya ; Forsberg, E. Camilla ; Carpenter, Susan
• Description:
  Our respiratory system is vital to protect us from the surrounding nonsterile environment; therefore, it is critical for a state of homeostasis to be maintained through a balance of inflammatory cues. Recent studies have shown that actively transcribed noncoding regions of the genome are emerging as key regulators of biological processes, including inflammation. | is one such example of an inflammatory inducible long intergenic noncoding RNA functioning to fine-tune immune gene expression. Using bulk and single-cell RNA sequencing, in addition to FACS, we find that | is most highly expressed in the lung and is most upregulated after LPS-induced lung injury (acute lung injury [ALI]) within alveolar macrophages, where it functions to regulate inflammation. We previously reported that | functions to regulate its neighboring protein Ptgs2 in |, and in this study, we use genetic mouse models to confirm its role in regulating gene expression more broadly in | during ALI. Il6, Ccl3, and Ccl5 are dysregulated in the |-deficient mice and can be rescued to wild type levels by crossing the deficient mice with our newly generated | transgenic mice, confirming that this gene functions in | Many genes are specifically regulated by | within alveolar macrophages originating from the bone marrow because the phenotype can be reversed by transplantation of wild type bone marrow into the |-deficient mice. In conclusion, we show that | is a |-acting long noncoding RNA that functions to regulate immune responses and maintain homeostasis within the lung at baseline and on LPS-induced ALI.
• Subjects:
  Acute Lung Injury Animals Cyclooxygenase 2 Disease Models, Animal Inflammation Lipopolysaccharides Macrophages, Alveolar Mice RNA, Long Noncoding
• Keywords:
  Alzheimer's Disease Alzheimer's Disease Sequencing Project Antiviral Agents Herpes Simplex Human Papillomavirus Torque Teno Viruses Whole Exome Sequencing Whole Genome Sequencing
• Source:
  J Immunol. 208(8):1886-1900
• Pubmed ID:
  35365562
• Pubmed Central ID:
  PMC9038212
• Document Type:
  Journal Article
• Funding:
  F31 HL151199/HL/NHLBI NIH HHSUnited States/ ; R01 DK100917/DK/NIDDK NIH HHSUnited States/ ; T32 GM008646/GM/NIGMS NIH HHSUnited States/ ; U01 IP000017/IP/NCIRD CDC HHSUnited States/
• Volume:
  208
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:7111ba6bd54d6e62b388397874212c39e014127d170b5c914b47555f94c19183e6b5a115699b37bde364a86261f8b6649f5f2fc9d4e70c02ab5df8954f12a1a6
• Download URL:
  https://stacks.cdc.gov/view/cdc/116861/cdc_116861_DS1.pdf
• File Type:
  [PDF - 2.56 MB ]