The genetic delivery of therapeutic monoclonal antibodies (mAbs) by in vivo production would be a new candidate for controlling virus infection, because it can overcome problems of high cost and limited supply in conventional protein-based antibody. We firstly performed electroporation using the plasmid encoding neutralizing IgG mAbs against hemagglutinin (HA) of A/PR/8/34 influenza virus (IAV) (EP). We succeeded to induce high level of neutralizing antibodies (approx.10 µg/ml) in mouse serum with a single dose for at least 70 days, and obtaining long-prophylactic effect against a lethal dose of IAV infection for 130 days. We next established a new method of passive immunotherapy after IAV infection. We performed hydrodynamic injection, which involve rapid injection of a large volume of plasmid-DNA solution into mice via the tail vein, using the neutralizing mAbs-expressing plasmids (HD). HD could more rapidly induce the mAbs in the serum than in EP. We also showed that a single HD could significantly protect the mice at least 2 days after the lethal dose of IAV infection.

 Radioprotective 105 (RP105) is an orphan TLR family member. The agonistic anti-RP105 mAb can provide the potent proliferation of B cells and adjuvant effect, inducing higher levels of antigen-specific antibodies compared to alum. We also generated genetic constructs of recombinant anti-RP105 mAb. By vaccination with the plasmids encoding anti-RP105 mAb and HA into mice, we obtained significantly HA-specific antibodies and observed protective effects against the lethal infection. Antibody gene transfer could thus provide a new therapeutic strategy targeting virus infection.

 After a severe burn injury, a severe and persistent systemic inflammatory syndrome develops that leads to a loss of skeletal muscle mass, otherwise referred to as muscle wasting. This is caused by the dynamic balance between skeletal muscle protein breakdown (proteolysis), skeletal muscle protein synthesis, and myogenesis being disturbed following the burn. Burns cause the activation of proteolytic processes, including the ubiquitin-proteasomal, autophagy, and apoptosis pathways; and this inhibits protein synthesis pathways, such as the insulin-like growth factor-1 pathway. Burns also inhibit skeletal muscle myogenesis by increasing the activity of negative regulators of myogenesis, such as myostatin. Furthermore, they induce neuroinflammation and motor neuron apoptosis. Because skeletal muscle atrophy induced in this way adversely affects both the survival and functional outcomes of patients, there is a need to develop novel strategies that target the molecular mechanisms involved in burn-induced skeletal muscle atrophy, such as those discussed in this review.

 Lipopolysaccharide (LPS), one of the cell surface components of Gram-negative bacteria, is recognized through receptorial complex TLR4/MD2 to activate innate immunity. LPS and its active principle lipid A are candidates for vaccine adjuvants which enhance the effectiveness of vaccines. On the other hand, most of bacterial LPS have inflammatory effects, for example, canonical Escherichia coli LPS has strong immune stimulative functions but it also shows lethal toxicity.

 Here, we focused on symbiotic bacterial lipid A as a pool of safe immune modulators. Alcaligenes faecalis inhabits in the human Peyer's patches without harmful effects and was suggested to be involved in the host immune system. Thus, we assumed that A. faecalis LPS and lipid A should not be toxic to the host. Kiyono et al. and we previously clarified that A. faecalis LPS has antibody-producing activity comparable to that of E. coli LPS without excessive inflammatory effect. In this study, we synthesized three types of A. faecalis lipid A with different acylation patterns via common disaccharide intermediate. After introduction of corresponding fatty acids to the disaccharide intermediate, two phosphate groups were simultaneously introduced and all protecting groups were removed to afford A. faecalis lipid A. Next, we evaluated their immunological function to identify hexa-acylated A. faecalis lipid A as active principle of A. faecalis LPS. Furthermore, hexa-acylated A. faecalis lipid A enhanced antigen-specific IgA antibody production without toxicity, and thus was found to be a promising adjuvant.

 Commensal microbes, airborne antigens/allergens, and food are all initially encountered in the oral cavity before entering into the gastrointestinal and often respiratory tracts. Similar to other mucosal sites, the local immune system is important for host defense in the oral mucosa. As an undergraduate, we reported the involvement of Suppressor of Cytokine Signaling (SOCS)1 in the augmenting effect of endotoxin shock by Muramyl Dipeptide (MDP), the minimal active structure of peptidoglycan. Furthermore, we studied the effects of bisphosphonates (bone resorption inhibitors) on pro-inflammatory and anti-inflammatory responses via macrophages. My post-graduate research interests include studying the mechanism by which saturated fatty acids, particularly palmitic acid, induce chronic inflammation in salivary glands and periodontal tissues through the innate immune system. In a recent study, we reported that proteins produced by salivary and lacrimal gland epithelial cells and senescence-associated CD4-positive T cells play crucial roles in the pathogenesis of dry mouth and dry eye. In this review, I summarize the research I have conducted until now.

 The evidence regarding the pathology and treatment of sepsis is insufficient, and there are many treatments that require further investigation. Based on this background, we conducted basic and clinical research conducted to control PAMPs (pathogen-associated molecular patterns), typified by endotoxin, and DAMPs (damage-associated molecular patterns), which are produced as a result of excessive innate immune responses associated with infectious diseases.

 First, we focused on the anti-inflammatory effects of recombinant thrombomodulin (rhTM), which has an anticoagulant effect, and investigated the relationship between histone H3, a DAMPs, and organ damage using a rat peritonitis sepsis model. The results revealed that rhTM neutralizes histone H3 and reduces renal damage. Then, using clinical data to examine the relationship between rhTM administration and renal damage, it was shown that rhTM significantly lowers blood purification dependence rate and improves renal prognosis. This was a corroborating result.

 Next, we focused on the fact that sepsis may be accompanied by hypogammaglobulinemia due to consumption or increased vascular permeability.

 There is still no unified opinion regarding the management of sepsis associated with hypogammaglobulinemia. Intravenous immunenoglobulin therapy (IVIG) is one of the treatment options, but it is not recommended in the guidelines due to insufficient evidence level. Therefore, when we conducted the study about the prognosis of hypogammaglobulinemia using data on patients with sepsis in the ICU, we found that the 28-day mortality rate increased. Furthermore, when we investigated the effectiveness of IVIG therapy for sepsis patients with low IgG level, we found that it improved the prognosis and was associated with an increase in renal replacement therapy-free days.

 Equisetum arvense extract (EA) exerts various biological effects, including anti-inflammatory activity. However, its impact on alveolar bone destruction has not been reported. In this review, we provide an overview of the histological characteristics of periodontal tissue and the mechanism of periodontal tissue destruction. Additionally, we propose a potential strategy for maintaining optimal oral hygiene based on our study, which highlights the inhibitory effects of EA on cytokine production and alveolar bone destruction induced by lipopolysaccharide (LPS).

 Topically applied LPS from gingival sulcus of rat induced cytokine production and osteoclastogenesis in periodontal tissue. Whereas locally administrated EA into the rat gingival sulcus reduced Tnf-α mRNA expression in the periodontal tissue caused by LPS-stimulation. Moreover, EA significantly decreased the number of cathepsin-K-positive osteoclasts by decreasing RANKL-expression and increasing OPG-expression in the periodontal ligament caused by LPS. The in vitro study showed that the upregulation of p-IκB kinase α and β (p-IKKα/β), p-NF-κB p65, TNF-α, interleukin-6, RANKL, and downregulation of semaphorin 3A (Sema3A), β-catenin, and OPG in the osteoblasts with LPS-stimulation improved with EA treatment. These findings demonstrated that topically applied EA suppressed alveolar bone resorption in the rat model with LPS-induced periodontitis by maintaining a balance in RANKL/OPG ratio via the pathways of NF-κB, Wnt/β -catenin, and Sema3A/Neuropilin-1. EA may prevent bone destruction by inhibiting osteoclastogenesis linked to cytokine bursts under plaque accumulation.

 Therefore, we believe that the pharmacological action of EA to control inflammation and/or bone destruction in periodontal tissues as a complemental strategy of daily brushing may be effective.