Saputra, Devina
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Yoon, Jin-Ha
(Institute for Occupational Health, Yonsei University College of Medicine)
,
Park, Hyunju
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Heo, Yongju
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Yang, Hyoseon
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Lee, Eun Ji
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Lee, Sangjin
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Song, Chang-Woo
(Inhalation Toxicology Center, Korea Institute of Toxicology)
,
Lee, Kyuhong
(Inhalation Toxicology Center, Korea Institute of Toxicology)
An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were gener...
An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-${\gamma}$ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be $12.5{\mu}g/m^3$) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions.
An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-${\gamma}$ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be $12.5{\mu}g/m^3$) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions.
* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.
제안 방법
(Seongnam, Korea) and were housed in a pathogen-free environment maintained at 19~26℃ and 50 ± 10% relative humidity with a 12 hr light-dark cycle. The mice were provided with rodent chow (PMI Lab Diet, USA) and UV-irradiated tap water ad libitum and were acclimatized for at least one week prior to beginning the study.
BLM was purchased from Nippon Kayaku (Tokyo, Japan). Eight-week-old mice were divided into 3 groups of 6 mice as follows: vehicle control group (saline + clean air), BLM-treated control group (BLM + clean air), and BLM-treated and CBNP-exposed group. On day 1, all mice were anesthetized with isoflurane and administered a 50-ml intratracheal dose of saline (group 1) or BLM 1 mg/kg (groups 2 and 3).
Gene transcripts were detected and quantified using SYBR Green (QuantiTect SYBR Green PCR Master Mix; Qiagen) according to the manufacturer’s instructions on a Rotor-Gene 6000 real-time rotary analyzer (Corbett Research, Sydney, Australia).
edu/). A melting curve analysis was performed on all amplified products to ensure the specificity and integrity of the PCR products. The transcript level of the beta-actin gene was used as an internal standard, and fold changes were calculated according to the 2 −ΔΔCT method (9).
Measurement of protein and mRNA expression levels in the lungs. To evaluate whether CBNP exposure induced an inflammatory response, we evaluated pro inflammatory cytokine levels in lung tissue homogenates. We found that the expression of IL-6 was significantly increased in the BLM control and BLM exposed groups compared to the control group (Fig.
데이터처리
All results are expressed as a mean ± standard error (SE). An analysis of variance (ANOVA) test was used to evaluate the significance of any differences between test groups. Dunnett’s multiple comparison test was used to compare the control group (VC) with experimental groups, and Bonferroni’s multiple comparison test was used to compare the BLM-treated, CBNPexposed group (BLM + CBNPs) to the BLM-treated control group (BC).
이론/모형
The presence of inflammatory mediators in the BAL fluid was analyzed by enzyme-linked immunosorbent assay (ELISA).The levels of interleukin-6 (IL-6) were measured using commercially available ELISA kits (R&D Systems, USA) according to the manufacturer’s protocol
The transcript level of the beta-actin gene was used as an internal standard, and fold changes were calculated according to the 2 −ΔΔCT method (9).
Dunnett’s multiple comparison test was used to compare the control group (VC) with experimental groups, and Bonferroni’s multiple comparison test was used to compare the BLM-treated, CBNPexposed group (BLM + CBNPs) to the BLM-treated control group (BC).
성능/효과
That study also reported a trend of increased health problems even when PM 2.5 levels were below 15 μg/m3, although the difference was not statistically significant.
참고문헌 (38)
1 Chiu K.H. Lee W.L. Chang C.C. Chen S.C. Chang Y.C. Ho M.N. Hsu J.F. Liao P.C. A label-free differential proteomic analysis of mouse bronchoalveolar lavage fluid exposed to ultrafine carbon black. Anal. Chim. Acta (2010) 673 160 166 10.1016/j.aca.2010.05.041 20599030
2 Simkó M. Mattsson M.O. Risks from accidental exposures to engineered nanoparticles and neurological health effects: a critical review. Part. Fibre Toxicol. (2010) 7 42 10.1186/1743-8977-7-42 21176150
3 Sager T.M. Castranova V. Surface area of particle administered versus mass in determining the pulmonary toxicity of ultrafine and fine carbon black: comparison to ultrafine titanium dioxide. Part. Fibre Toxicol. (2009) 6 15 10.1186/1743-8977-6-15 19413904
5 Lin W. Huang W. Zhu T. Hu M. Brunekreef B. Zhang Y. Liu X. Cheng H. Gehring U. Li C. Tang X. Acute respiratory inflammation in children and black carbon in ambient air before and during the 2008 Beijing Olympics. Environ. Health Perspect. (2011) 119 1507 1512 10.1289/ehp.1103461 21642045
6 Ramage L. Guy K. Expression of C-reactive protein and heat-shock protein-70 in the lung epithelial cell line A549, in response to PM10 exposure. Inhalation Toxicol. (2004) 16 447 452 10.1080/08958370490439614
7 Donaldson K. Stone V. MacNee W. The toxicology of ultrafine particles (In: Maynard RL, Howard CV, Eds). Particulate matter: properties and effects upon health. Bios Scientific Oxford (1999)
8 Tong H. McGee J.K. Saxena R.K. Kodavanti U.P. Devlin R.B. Gilmour M.I. Influence of acid functionalization on the cardiopulmonary toxicity of carbon nanotubes and carbon black particles in mice. Toxicol. Appl. Pharmacol. (2009) 239 224 232 10.1016/j.taap.2009.05.019 19481103
9 Donaldson K. Stone V. Clouter A. Renwick L. Mac-Nee W. Ultrafine particles. Occup. Environ. Med. (2001) 58 211 216 10.1136/oem.58.3.211 11171936
10 Bourdon J.A. Halappanavar S. Saber A.T. Jacobsen N.R. Williams A. Wallin H. Vogel U. Yauk C.L. Hepatic and pulmonary toxicogenomic profiles in mice intratracheally instilled with carbon black nanoparticles reveal pulmonary inflammation, acute phase response, and alterations in lipid homeostasis. Toxicol. Sci. (2012) 127 474 484 10.1093/toxsci/kfs119 22461453
11 Tomimori Y. Muto T. Saito K. Tanaka T. Maruoka H. Sumida M. Fukami H. Fukuda Y. Involvement of mast cell chymase in bleomycin-induced pulmonary fibrosis in mice. Eur. J. Pharmacol. (2003) 478 179 185 10.1016/j.ejphar.2003.08.050 14575803
12 Decologne N. Wettstein G. Kolb M. Margetts P. Garrido C. Camus P. Bonniaud P. Bleomycin induces pleural and subpleural fibrosis in the presence of carbon particles. Eur. Respir. J. (2010) 35 176 185 10.1183/09031936.00181808 19574324
13 Zhou X.M. Zhang G.C. Li J.X. Hou J. Inhibitory effects of Hu-qi-yin on the bleomycin-induced pulmonary fibrosis in rats. J. Ethnopharmacol. (2007) 111 255 264 10.1016/j.jep.2006.11.029 17188826
14 Kamata H. Tasaka S. Inoue K. Miyamoto K. Nakano Y. Shinoda H. Kimizuka Y. Fujiwara H. Ishii M. Hasegawa N. Takamiya R. Fujishima S. Takano H. Ishizaka A. Carbon black nanoparticles enhance bleomycininduced lung inflammatory and fibrotic changes in mice. Exp. Biol. Med. (Maywood) (2011) 236 315 324 10.1258/ebm.2011.010180 21427237
15 Li Y.J. Azuma A. Usuki J. Abe S. Matsuda K. Sunazuka T. Shimizu T. Hirata Y. Inagaki H. Kawada T. Takahashi S. Kudoh S. Omura S. EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-beta signaling in lung fibroblasts. Respir. Res. (2006) 7 16 10.1186/1465-9921-7-16 16438734
16 Vesterdal L.K. Folkmann J.K. Jacobsen N.R. Sheykhzade M. Wallin H. Loft S. Moller P. Pulmonary exposure to carbon black nanoparticles and vascular effects. Part. Fibre Toxicol. (2010) 7 33 10.1186/1743-8977-7-33 21054825
17 Gu J. Bai Z. Liu A. Wu L. Xie Y. Li W. Dong H. Zhang X. Characterization of Atmospheric Organic Carbon and Element Carbon of PM 2.5 and PM 10 at Tianjin, China. Aerosol Air Qual. Res. (2010) 10 167 176
18 Seinfeld J.H. Pandis S.N Atmospheric chemistry and physics: From air pollution to climate change, John Wiley New York (1998) 1 1232
19 Kim S.N. Lee J. Yang H.S. Cho J.W. Kwon S. Kim Y.B. Her J.D. Cho K.H. Song C.W. Lee K. Dose-response Effects of Bleomycin on Inflammation and Pulmonary Fibrosis in Mice. Toxicol. Res. (2010) 26 217 222 10.5487/TR.2010.26.3.217 24278527
20 Rybkin I.I. Zhou Y. Volaufova J. Smagin G.N. Ryan D.H. Harris R.B. Effect of restraint stress on food intake and body weight is determined by time of day. Am. J. Physiol. (1997) 273 1612 1622
21 Harris R.B. Zhou J. Youngblood B.D. Rybkin I.I. Smagin G.N. Ryan D.H. Effect of repeated stress on body weight and body composition of rats fed low- and highfat diets. Am. J. Physiol. (1998) 275 R1928 1938 9843882
22 Smith R.E. Strieter R.M. Phan S.H. Lukacs N. Kunkel S.L. TNF and IL-6 mediate MIP-1alpha expression in bleomycin-induced lung injury. J. Leukocyte Biol. (1998) 64 528 536 9766634
23 Moeller A. Ask K. Warburton D. Gauldie J. Kolb M. The bleomycin animal model: a useful tool to investigate treatment options for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol. (2008) 40 362 382 10.1016/j.biocel.2007.08.011 17936056
24 Hernnäs J. Nettelbladt O. Bjermer L. Särnstrand B. Malmström A. Hällgren R. Alveolar accumulation of fibronectin and hyaluronan precedes bleomycininduced pulmonary fibrosis in the rat. Eur. Respir. J. (1992) 5 404 410 1373389
25 Chen Y.L. Zhang X. Bai J. Gai L. Ye X.L. Zhang L. Xu Q. Zhang Y.X. Xu L. Li H.P. Ding X. Sorafenib ameliorates bleomycin-induced pulmonary fibrosis: potential roles in the inhibition of epithelial-mesenchymal transition and fibroblast activation. Cell Death Dis. (2013) 4 e665 10.1038/cddis.2013.154 23764846
26 Zhao J. Shi W. Wang Y.L. Chen H. Bringas P. Jr. Datto M.B. Frederick J.P. Wang X.F. Warburton D. Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. (2002) 282 L585 593 11839555
27 Segel M.J. Izbicki G. Cohen P.Y. Or R. Christensen T.G. Wallach-Dayan S.B. Breuer R. Role of interferon-gamma in the evolution of murine bleomycin lung fibrosis. Am. J. Physiol. Lung Cell. Mol. Physiol. (2003) 285 L1255 1262 10.1152/ajpcell.00149.2003 12857673
28 Kikuchi N. Ishii Y. Morishima Y. Yageta Y. Haraguchi N. Itoh K. Yamamoto M. Hizawa N. Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance. Respir. Res. (2010) 11 31 10.1186/1465-9921-11-31 20298567
29 Kushwah R. Gagnon S. Sweezey N.B. T cell unresponsiveness in a pediatric cystic fibrosis patient: a case report. Allergy Asthma Clin. Immunol. (2014) 10 2 10.1186/1710-1492-10-2 24438707
31 Niwa Y. Hiura Y. Sawamura H. Iwai N. Inhalation exposure to carbon black induces inflammatory response in rats. Circ. J. (2008) 72 144 149 10.1253/circj.72.144 18159116
32 Adamson I.Y. Prieditis H.L. Response of mouse lung to carbon deposition during injury and repair. Environ. Health Perspect. (1995) 103 72 76 10.1289/ehp.9510372 7543046
34 Inoue K. Yanagisawa R. Koike E. Nakamura R. Ichinose T. Tasaka S. Kiyono M. Takano H. Effects of carbon black nanoparticles on elastase-induced emphysematous lung injury in mice. Basic Clin. Pharmacol. Toxicol. (2011) 108 234 240 10.1111/j.1742-7843.2010.00638.x 21266011
35 Alexander D.J. Collins C.J. Coombs D.W. Gilkison I.S. Hardy C.J. Healey G. Karantabias G. Johnson N. Karlsson A. Kilgour J.D. McDonald P. Association of Inhalation Toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals. Inhalation Toxicol. (2008) 20 1179 1189 10.1080/08958370802207318
36 Begum B.A. Hossain A. Nahar N. Markwitz A. Hopke P.K. Organic and Black Carbon in PM2.5 at an Urban Site at Dhaka, Bangladesh. Aerosol Air Qual. Res. (2012) 12 1062 1072
37 Won S.R. Lim J.Y. Shim I.K. Kim E.J. Choi A.R. Han J.S. Lee W.S. Characterization of PM 2.5 and PM 10 concentration distribution at public facilities in Korea. J. Korean Soc. Indoor Environ. (2012) 9 229 238
38 Franklin M. Zeka A. Schwartz J. Association between PM2.5 and all-cause and specific-cause mortality in 27 US communities. J. Exposure Sci. Environ. Epidemiol. (2007) 17 279 287 10.1038/sj.jes.7500530
※ AI-Helper는 부적절한 답변을 할 수 있습니다.