title: Insect cytokine paralytic peptide (PP) induces cellular and humoral immune responses in the silkworm Bombyx mori.
abstract: In the blood (hemolymph) of the silkworm Bombyx mori, the insect cytokine paralytic peptide (PP) is converted from an inactive precursor to an active form in response to the cell wall components of microorganisms and contributes to silkworm resistance to infection. To investigate the molecular mechanism underlying the up-regulation of host resistance induced by PP, we performed an oligonucleotide microarray analysis on RNA of blood cells (hemocytes) and fat body tissues of silkworm larvae injected with active PP. Expression levels of a large number of immune-related genes increased rapidly within 3 h after injecting active PP, including phagocytosis-related genes such as tetraspanin E, actin A1, and ced-6 in hemocytes, and antimicrobial peptide genes cecropin A and moricin in the fat body. Active PP promoted in vitro and in vivo phagocytosis of Staphyloccocus aureus by the hemocytes. Moreover, active PP induced in vivo phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) in the fat body. Pretreatment of silkworm larvae with ML3403, a pharmacologic p38 MAPK inhibitor, suppressed the PP-dependent induction of cecropin A and moricin genes in the fat body. Injection of active PP delayed the killing of silkworm larvae by S. aureus, whereas its effect was abolished by preinjection of the p38 MAPK inhibitor, suggesting that p38 MAPK activation is required for PP-dependent defensive responses. These findings suggest that PP acts on multiple tissues in silkworm larvae and acutely activates cellular and humoral immune responses, leading to host protection against infection.
authors.affiliation: Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Kamimura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Noda
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Imamura
authors.forename: Kazuei
authors.initials: K
authors.lastname: Mita
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D000818:Animals; D012831:Bombyx / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006434:Hemocytes / Q000276:immunology* / Q000378:metabolism; D006458:Hemolymph / Q000276:immunology / Q000378:metabolism; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects* / Q000276:immunology; D019476:Insect Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D007814:Larva / Q000276:immunology / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D016207:Cytokines; D019476:Insect Proteins; D009479:Neuropeptides; C121924:paralytic peptide, insect