Hiroyuki Kishi: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Masamichi Sato: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Yoko Shibata: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan. ORCID
Kento Sato: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Sumito Inoue: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Shuichi Abe: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Tomomi Kimura: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Michiko Nishiwaki: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Keiko Yamauchi: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Takako Nemoto: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Akira Igarashi: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Yoshikane Tokairin: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
Osamu Nakajima: Research Laboratory for Molecular Genetics, School of Medicine, Yamagata University, Yamagata City, Yamagata Japan.
Isao Kubota: Department of Cardiology, Pulmonology, and Nephrology, School of Medicine, Yamagata University, Yamagata City, Yamagata 990-9585 Japan.
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.
