IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by α1-antitrypsin in Mouse Bone Marrow Cells.
- Author:
Siyoung LEE
1
;
Dong Ki CHOI
;
Areum KWAK
;
Sinae KIM
;
Tam Thanh NGUYEN
;
Gaae GIL
;
Eunhye KIM
;
Kwang Ha YOO
;
In Ae KIM
;
Youngmin LEE
;
Hyunjhung JHUN
;
Edward D CHAN
;
Xiyuan BAI
;
Hyunwoo KIM
;
Yong Sung KIM
;
Soohyun KIM
Author Information
- Publication Type:Brief Communication
- Keywords: Interleukin-32; Mouse bone marrow cell; Proteinase 3; Interleukin-6; Recombinant AAT-Fc
- MeSH: Animals; Bone Marrow Cells*; Bone Marrow*; Cytokines*; Graft vs Host Disease; Humans; Inflammation; Interleukin-6; Interleukins; Membranes; Mice*; Myeloblastin; Myeloid Cells; Serine Proteases
- From:Immune Network 2017;17(2):116-120
- CountryRepublic of Korea
- Language:English
- Abstract: The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.
