Splenic Dendritic Cells Induced by Oral Antigen Administration Are Important for the Transfer of Oral Tolerance in an Experimental Model of Asthma

Nagatani, Katsuya; Dohi, Makoto; To, Yasuo; Tanaka, Ryoichi; Okunishi, Katsuhide; Nakagome, Kazuyuki; Sagawa, K; Tanno, Yudo; Komagata, Yoshinori; Yamamoto, Kazuhiko

doi:10.4049/jimmunol.176.3.1481

Cited by 24 publications

(19 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CD11b MicroBeads (Miltenyi Biotec, Auburn, CA) were able to specifically bind with macrophages in mouse, by which method the macrophages in spleen were isolated using magnetic-activated cell sorting (MACS) techniques (43). The same approach was applied in the present study to isolate AMs from BAL cells.…”

Section: Methodsmentioning

confidence: 99%

Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice

Xu¹,

Xu²,

Barrett³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

stase (MMP-12), mainly produced by macrophages, has been shown to play a key role in the pathogenesis of emphysema in animal models. Chronic cigarette smoke increases pulmonary MMP-12, which is closely correlated with an elevation of pulmonary substance P (SP). Because alveolar macrophages (AMs) contain the neurokinin-1 receptor (NK1R), we tested whether SP was able to trigger the upregulation of MMP-12 synthesis in AMs by acting on the NK1R. AMs isolated from bronchoalveolar lavage cells in C3H/HeN mice were cultured with control medium or SP that was coupled without or with NK1R antagonists (CP-99,994 or aprepitant) for 24 h. We found that SP significantly increased the mRNA of MMP-12 and NK1R by 11-fold and 82%, respectively, in AMs (P Ͻ 0.05), and these responses were abolished by NK1R antagonists with little change in the cells' viability. Because pulmonary SP is primarily released by bronchopulmonary C-fibers (PCFs), we further asked whether destruction of PCFs would reduce SP and MMP-12. Two groups of mice were pretreated with vehicle and neonatal capsaicin (NCAP) to degenerate PCFs, respectively. Our results show that NCAP treatment significantly decreased mRNA and protein levels of SP associated with a reduction NK1R and MMP-12 in the lungs and AMs. These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs. emphysema; neurokinin-1 receptor; bronchopulmonary C-fibers; matrix metalloproteinase-12; chronic obstructive pulmonary disease METALLOELASTASE (MMP-12) is able to degrade many kinds of extracellular matrix proteins, including elastin (16). Loss of elastic recoil and damage of elastic fibers along with histological changes of emphysema implicate elastin degradation as an important factor in the pathogenesis of chronic obstructive pulmonary disease (COPD) (38). MMP-12 is increased in lung tissue (5) and macrophages (6) of cigarette smoke (CS)-exposed mice and in sputum from COPD patients (7, 40). Furthermore, an increase of the ratio of MMP-12 to the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) was also observed in COPD animal models (61). TIMP-1 can inhibit all matrix metalloproteinases (MMPs), including MMP-12, resulting in loss of proteolytic activity (27,54). Most importantly, MMP-12 gene-deficient mice do not develop emphysema after chronic CS exposure (19). Conversely, overexpression of MMP-12 in transgenic mice is associated with spontaneous development of pulmonary emphysema (41). Together, these results strongly suggest that MMP-12 plays a key role in the pathogenesis of COPD, at least in animal models. Substance P (SP) is a proinflammatory neuropeptide and neurogenic mediator with a high affinity for binding to the neurokinin-1 receptor (NK1R) (48). Previous studies have shown three lines of evidence implying the possible SP modulatory effects on pulmonary MMP-12. First, significantly correlated increases of pulmonary SP and MMP-12 have been observed in CS-exposed mice (61). Second, alveolar macrophages (AMs...

show abstract

Section: Methodsmentioning

confidence: 99%

Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice

Xu¹,

Xu²,

Barrett³

2008

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…57 Briefly, the mice were euthanized and the lungs were lavaged with 0.5 ml sterile PBS for 4 times, and the lavage fluid was centrifuged, followed by collection for detection of cytokines or stored at ¡80 C until use. After suspending the pellet with PBS, the cells were counted and subjected to alveolar macrophages isolation as described.…”

Section: Intratracheal Administration Of Lentivirusmentioning

confidence: 99%

Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination

Feng

Zhao

et al. 2014

Autophagy

View full text Add to dashboard Cite

These authors contribute equally to this work.Keywords: autophagy, BECN1, protein degradation, RNF216, ubiquitination Abbreviations: Atg, autophagy-related; BALF, bronchoalveolar lavage fluid; BMDM, bone marrow-derived macrophage; CFU, colony-forming unit; GFP, green fluorescent protein; HRP, horseradish peroxidase; i.t., intratracheally; LPS, lipopolysaccharide; MAP1LC3A, microtubule-associated protein 1 light chain 3 a; MOI, multiplicity of infection; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B-cells; PBS, phosphate-buffered saline; RIPK1, receptor (TNFRSF)-interacting serine-threonine kinase 1; RNF216, ring finger protein 216;TIRAP, toll-interleukin 1 receptor (TIR) domain containing adaptor protein; TLR, toll-like receptor; TNF, tumor necrosis factor; TRAF, TNF receptor-associated factor; TICAM1/TRIF, toll-like receptor adaptor molecule 1; TICAM2, toll-like receptor adaptor molecule 2; shRNA, short hairpin RNA; Triad, 2 RING fingers and a DRIL (double RING finger linked); Ub, ubiquitin.Autophagy is an evolutionarily conserved biological process involved in an array of physiological and pathological events. Without proper control, autophagy contributes to various disorders, including cancer and autoimmune and inflammatory diseases. It is therefore of vital importance that autophagy is under careful balance. Thus, additional regulators undoubtedly deepen our understanding of the working network, and provide potential therapeutic targets for disorders. In this study, we found that RNF216 (ring finger protein 216), an E3 ubiquitin ligase, strongly inhibits autophagy in macrophages. Further exploration demonstrates that RNF216 interacts with BECN1, a key regulator in autophagy, and leads to ubiquitination of BECN1, thereby contributing to BECN1 degradation. RNF216 was involved in the ubiquitination of lysine 48 of BECN1 through direct interaction with the triad (2 RING fingers and a DRIL [double RING finger linked]) domain. We further showed that inhibition of autophagy through overexpression of RNF216 in alveolar macrophages promotes Listeria monocytogenes growth and distribution, while knockdown of RNF216 significantly inhibited these outcomes. These effects were confirmed in a mouse model of L. monocytogenes infection, suggesting that manipulating RNF216 expression could be a therapeutic approach. Thus, our study identifies a novel negative regulator of autophagy and suggests that RNF216 may be a target for treatment of inflammatory diseases.

show abstract

“…The BALF was centrifuged 1500 rpm at 4°C for 10 minutes, and the level of protein in the supernatant was measured using Bradford total protein assay (Bio-Rad Laboratories Inc., Hercules, CA). 21 The cells were resuspended in 1 ml of saline with 1% bovine serum albumin (Sigma-Aldrich, St. Louis, MO) and the total cell numbers were counted with a hemocytometer. Cytospin samples were prepared by centrifuging the suspensions at 350 rpm for 10 minutes and cell differentials were determined by counting at least 300 leukocytes on Giemsa Stain (Wako Pure Chemical Industries, Ltd.).…”

Section: Analysis Of Balfmentioning

confidence: 99%

Neutrophil Elastase Contributes to Acute Lung Injury Induced by Bilateral Nephrectomy

Ishii

Doi

Okamoto

et al. 2010

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a serious problem in critically ill patients of intensive care units. It has been reported previously that AKI can induce acute lung injury (ALI), as well as cause injuries to other remote organs , including the lungs. Patients with AKI complicated by ALI show remarkably high mortality. ALI is characterized by neutrophil infiltration into the lung. Neutrophil elastase (NE) is a key enzyme for tissue injury caused by activated neutrophils , such as occurs in ALI. Therefore , this study investigated the role of NE in AKI-induced ALI using a specific NE inhibitor , sivelestat sodium hydrate (ONO-5046), in a mouse bilateral nephrectomy model. Bilateral nephrectomy showed not only a remarkable increase in blood urea nitrogen levels, but also demonstrated neutrophil infiltration into the lung, increased pulmonary inflammatory cytokine expression [interleukin-6, neutrophil chemokine keratinocyte-derived chemokine, and tumor necrosis factor-␣], and protein leakage with early increases in both systemic and pulmonary NE activity. ONO-5046 treatment reduced NE activity and improved these pulmonary inflammatory responses. Additionally, ONO-5046-treated animals had longer survival times. These data demonstrate that increasing NE activity induces pulmonary inflammatory damage in a bilateral nephrectomy model. Blockade of NE activity will be a useful therapeutic strategy for ALI complications in AKI patients. Acute lung injury (ALI) is a life-threatening condition that is frequently complicated with acute kidney injury (AKI), which is a serious condition in intensive care units. The ALI mortality is higher than 50% and increases with the development of other organ failure including AKI.1 One report described a mortality rate higher than 80% for patients with AKI complicated with ALI.2 Current prevention and treatment strategies for AKI cannot sufficiently improve the mortality of these severely ill patients. Although many basic and clinical researchers are investigating novel therapies for AKI, 3 targeting of other organ damages caused by AKI is also necessary for improving AKI outcomes.Recently, it has been suggested that AKI influences other remote organs including the lungs.4 -6 Experimental evidence indicates that AKI-induced ALI occurs not only by volume overload, but also through deleterious kidneylung interactions. Mechanisms of AKI-induced ALI include dysregulation of inflammatory reaction, innate immune response, oxidative stress, apoptosis, and soluble mediator metabolism.7 Rodent models of bilateral nephrectomy (BNx) and renal ischemia reperfusion have been used to investigate the role of AKI in the pathogenesis of ALI. 8 -11 Ischemic AKI engenders increased pulmonary vascular permeability by down-regulating pulmonary epithelial sodium channel, Na,K-ATPase, and aquaporin-5. 10 Ischemic AKI induced leukocyte accumulation and activation of inflammatory transcription factors such as nuclear factor-B and p38 mitogen-activated protein kinase in the lung, which was attenuated by an anti-infla...

show abstract

Splenic Dendritic Cells Induced by Oral Antigen Administration Are Important for the Transfer of Oral Tolerance in an Experimental Model of Asthma

Cited by 24 publications

References 46 publications

Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice

Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice

Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination

Neutrophil Elastase Contributes to Acute Lung Injury Induced by Bilateral Nephrectomy

Contact Info

Product

Resources

About