title: Role of chemokine C-C motif ligand-1 in acute and chronic pulmonary inflammations.
abstract: BACKGROUND
  Chemokine C-C motif ligand 1 (CCL1) accumulates C-C motif chemokine receptor 8 positive leukocytes to the inflammatory sites. Single-nucleotide polymorphisms in the chemokine CCL1 gene are associated with exacerbation of chronic obstructive lung disease. However, it is unclear whether CCL1 has immunomodulatory functions during pulmonary inflammation. This study aimed to elucidate this issue using newly generated transgenic mice that express CCL1 in the lungs (SPC-CCL1 mice).
  
  
  METHODS
  To evaluate the phenotypes of these mice, lung section and bronchoalveolar lavage (BAL) fluid analyses were performed. We intratracheally administered lipopolysaccharide (LPS) or Mycobacterium bovis as a model of acute or chronic lung inflammation, respectively.
  
  
  RESULTS
  No histological differences were observed between lung tissue from SPC-CCL1 Tg and wild-type mice in the resting condition and after LPS administration. In the resting condition, the total BAL cell concentration was lower in SPC-CCL1 Tg mice than in wild-type mice (P = 0.0097). Flow cytometric analyses showed that SPC-CCL1 Tg mice had fewer F4/80-positive cells than wild-type mice (P = 0.0278). After intratracheal LPS administration, CCL1 overexpression changed neither the total numbers nor population of BAL cells. After mycobacterial administration, pulmonary granuloma formation was significantly enhanced. The degree of Immunostaining for endoplasmic reticulum to nucleus signaling 1, a molecule associated with granuloma formation and endoplasmic reticulum stress, was significantly enhanced in the granuloma regions of SPC-CCL1 mice treated with Mycobacterium, compared to those of wild-type mice.
  
  
  CONCLUSIONS
  CCL1 overexpression in the lungs did not change the acute inflammatory response induced by LPS, but enhanced granuloma formation after mycobacterial treatment, possibly through enhancing endoplasmic reticulum stress.
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Sato
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Yoko
authors.identifier: 0000-0003-1794-0026
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Sumito
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Nishiwaki
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamauchi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Nemoto
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Igarashi
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Yoshikane
authors.initials: Y
authors.lastname: Tokairin
authors.affiliation: Research Laboratory for Molecular Genetics, School of Medicine, Yamagata University, Yamagata City, Yamagata Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nakajima
authors.affiliation: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
keywords: CCL1; Endoplasmic reticulum stress; Gene targeted mouse; Granuloma; Lipopolysaccharide; Mycobacterium bovis