title: Myeloid ZFP36L1 does not regulate inflammation or host defense in mouse models of acute bacterial infection.
abstract: Zinc finger protein 36, C3H type-like 1 (ZFP36L1) is one of several Zinc Finger Protein 36 (Zfp36) family members, which bind AU rich elements within 3' untranslated regions (UTRs) to negatively regulate the post-transcriptional expression of targeted mRNAs. The prototypical member of the family, Tristetraprolin (TTP or ZFP36), has been well-studied in the context of inflammation and plays an important role in repressing pro-inflammatory transcripts such as TNF-α. Much less is known about the other family members, and none have been studied in the context of infection. Using macrophage cell lines and primary alveolar macrophages we demonstrated that, like ZFP36, ZFP36L1 is prominently induced by infection. To test our hypothesis that macrophage production of ZFP36L1 is necessary for regulation of the inflammatory response of the lung during pneumonia, we generated mice with a myeloid-specific deficiency of ZFP36L1. Surprisingly, we found that myeloid deficiency of ZFP36L1 did not result in alteration of lung cytokine production after infection, altered clearance of bacteria, or increased inflammatory lung injury. Although alveolar macrophages are critical components of the innate defense against respiratory pathogens, we concluded that myeloid ZFP36L1 is not essential for appropriate responses to bacteria in the lungs. Based on studies conducted with myeloid-deficient ZFP36 mice, our data indicate that, of the Zfp36 family, ZFP36 is the predominant negative regulator of cytokine expression in macrophages. In conclusion, these results imply that myeloid ZFP36 may fully compensate for loss of ZFP36L1 or that Zfp36l1-dependent mRNA expression does not play an integral role in the host defense against bacterial pneumonia.
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Lynnae D
authors.initials: LD
authors.lastname: Hyatt
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Wasserman
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Yoon J
authors.initials: YJ
authors.lastname: Rah
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Kori Y
authors.initials: KY
authors.lastname: Matsuura
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Fadie T
authors.initials: FT
authors.lastname: Coleman
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Hilliard
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Zachary Ash
authors.initials: ZA
authors.lastname: Pepper-Cunningham
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Ieong
authors.affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Stumpo
authors.affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, United States of America; Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Perry J
authors.initials: PJ
authors.lastname: Blackshear
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Quinton
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Mizgerd
authors.affiliation: Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, United States of America; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Jones
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism* / Q000382:microbiology; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D051817:Butyrate Response Factor 1; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000382:microbiology; D008168:Lung / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism / Q000382:microbiology; D009687:Nuclear Proteins / Q000378:metabolism*; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: D051817:Butyrate Response Factor 1; D016207:Cytokines; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C488431:Zfp36l1 protein, mouse