Preventive effect of Imperatorin on acute lung injury induced by lipopolysaccharide in mice

Imperatorin, a linear furanocoumarin, has many pharmacological effects such as antibacterial, anti-inflammatory and antiviral effects. The purpose of this study was to investigate the effect of Imperatorin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. BALB/c mice were pretreated with Imperatorin 1 h before LPS challenge. We found that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) were decreased significantly, and the level of interleukin-10 (IL-10) was up-regulated 8 h after Imperatorin treatment. Pretreatment with Imperatorin (15 or 30 mg/kg) decreased lung wet-to-dry weight (W/D) ratio, the number of inflammatory cells and myeloperoxidase (MPO) activities. Additionally, Imperatorin attenuated lung histopathological changes and significantly inhibited the phosphorylation of IκB, JNK, ERK and p38/MAPK. These findings demonstrate that Imperatorin protects against LPS-induced ALI in mice.     

Protective effect of taraxasterol on acute lung injury induced by lipopolysaccharide in mice

Taraxasterol, a pentacyclic-triterpene isolated from Taraxacum officinale, has been reported to have potent anti-inflammatory properties. However, the effect of taraxasterol on lipopolysaccharide (LPS)-induced mice acute lung injury has not been investigated. The aims of this study were to investigate whether taraxasterol could ameliorate the inflammation response in LPS-induced acute lung injury and to clarify the possible mechanism. Male BALB/c mice were pretreated with taraxasterol 1 h before intranasal instillation of LPS. 7 h after LPS administration, the myeloperoxidase (MPO) in lung tissues, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were detected. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were determined by western blotting. The results showed that taraxasterol attenuated the infiltration of inflammatory cells, the activity of myeloperoxidase (MPO), lung wet/dry ratio, and the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in a dose-dependent manner. Additionally, western blotting results showed that taraxasterol inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. Our data suggest that anti-inflammatory effects of taraxasterol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPK signaling pathways.     

Standardized myrtol attenuates lipopolysaccharide induced acute lung injury in mice

Context: Standardized myrtol, an essential oil containing primarily cineole, limonene and α-pinene, has been used for treating nasosinusitis, bronchitis and chronic obstructive pulmonary disease (COPD).

Objective: To investigate the effects of standardized myrtol in a model of acute lung injury (ALI) induced by lipopolysaccharides (LPS).

Materials and methods: Male BALB/c mice were treated with standardized myrtol for 1.5?h prior to exposure of atomized LPS. Six hours after LPS challenge, lung injury was determined by the neutrophil recruitment, cytokine levels and total protein concentration in the bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in the lung tissue. Additionally, pathological changes and NF-κB activation in the lung were examined by haematoxylin and eosin staining and western blot, respectively.

Results: In LPS-challenged mice, standardized myrtol at a dose of 1200?mg/kg significantly inhibited the neutrophile counts (from 820.97?±?142.44 to 280.42?±?65.45, 10³/mL), protein concentration (from 0.331?±?0.02 to 0.183?±?0.01, mg/mL) and inflammatory cytokines level (TNF-α: from 6072.70?±?748.40 to 2317.70?±?500.14, ng/mL; IL-6: from 1184.85?±?143.58 to 509.57?±?133.03, ng/mL) in BALF. Standardized myrtol also attenuated LPS-induced MPO activity (from 0.82?±?0.04 to 0.48?±?0.06, U/g) and pathological changes (lung injury score: from 11.67?±?0.33 to 7.83?±?0.79) in the lung. Further study demonstrated that standardized myrtol prevented LPS-induced NF-κB activation in lung tissues.

Discussion and conclusion: Together, these data suggest that standardized myrtol has the potential to protect against LPS-induced airway inflammation in a model of ALI.     

非诺贝特改善脂多糖诱导的急性肺损伤及其机制研究

摘要：目的　探究非诺贝特（Fen）对急性肺损伤（ALI）的作用及机制。方法　（1）体内实验。30只C57BL/6雄性小鼠采用随机数字表法分成6组：正常组,模型组（LPS组）,阳性药地塞米松（DXMS）组,Fen低、中、高剂量（20、40、80 mg/kg）组。分组给药12 h后,收集肺泡灌洗液（BALF）,处死小鼠,获取肺组织,记录肺组织湿/干质量比;酶联免疫吸附试验（ELISA）检测肺组织肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-1β含量;BCA比色法和瑞氏-吉姆萨染色检测BALF中总蛋白含量和免疫细胞数目;苏木精-伊红（HE）染色观察肺组织病变并进行病理评分。Western blot检测肺组织B淋巴细胞瘤-2蛋白（Bcl-2）、Bcl-2相关X蛋白（Bax）及c-Jun氨基末端激酶（JNK）、磷酸化JNK（p-JNK）表达。（2）体外实验。实验设Control、LPS（10 mg/L）、LPS+Fen（5 μmol/L）、LPS+Fen（10 μmol/L）、LPS+Fen（20 μmol/L）组。A549细胞经LPS（10 mg/L）处理后分别加入5、10、20 μmol/L的Fen处理12 h,分别用DCFH-DA、Annexin V-FITC/PI法和Western blot检测Fen对A549细胞ROS、凋亡和凋亡相关蛋白Bcl-2、Bax及p-JNK影响。另选取LPS（10 mg/L）+Fen（20 μmol/L）处理后添加H2O2（100 μmol/L）,观察细胞ROS、凋亡率和凋亡相关蛋白Bcl-2、Bax表达变化。此外,选取LPS（10 mg/L）+Fen（20 μmol/L）处理后添加JNK激动剂Anisomycin（3 μmol/L）,观察Bcl-2、Bax表达变化。结果　（1）与正常组相比,模型组小鼠肺组织湿/干质量比,肺组织损伤评分,TNF-α、IL-6、IL-1β含量,肺泡灌洗液总蛋白含量,免疫细胞数目,p-JNK和Bax表达均出现显著升高,Bcl-2表达显著降低。与模型组相比,Fen低、中、高剂量组上述指标变化均被逆转。（2）Fen能显著减少LPS诱导的A549细胞ROS含量,降低凋亡率,抑制p-JNK和Bax表达并促进Bcl-2表达。H2O2可逆转Fen引起的上述效应。Anisomycin也能抑制Fen引起的Bcl-2上调和Bax蛋白下调。结论　Fen可通过ROS/JNK信号抑制细胞凋亡,从而减轻ALI。     

蛹虫草提取物对内毒素引起小鼠急性肺损伤的保护作用

目的 :观察蛹虫草提取物对内毒素引起小鼠急性肺损伤的保护作用。方法 :建立内毒素急性损伤小鼠肺病理模型 ,造模 4和 8h后 ,用蛹虫草提取物治疗 ,造模 2 4h后 ,对血细胞和肺灌洗液中细胞进行计数并测定肺灌洗液中蛋白酶的活性和蛋白的含量。结果 :蛹虫草提取物对血液成分没有明显影响 ,但可以使肺灌洗液中白细胞、粒细胞的含量有所降低 ,而淋巴细胞和单核细胞的数量有所增加 ,蛋白酶活性降低。结论 :蛹虫草提取物可调节机体组织的免疫功能 ,可以缓解由于内毒素或类似物质造成的肺部炎症 ,具有一定的肺保护作用。     

Effect of 15-deoxy-delta 12,14-prostaglandin J2 on acute lung injury induced by lipopolysaccharide in mice

15-Deoxy-delta(12,14)-prostaglandin J(2) (15d-prostaglandin J(2)) has received attention for its anti-inflammatory properties. The present study investigated the efficacy of 15d-prostaglandin J(2) on acute lung injury induced by lipopolysaccharide in mice. ICR mice were administered with 15d-prostaglandin J(2) (10 microg/kg, 100 microg/kg, or 1 mg/kg) before intratracheal challenge with lipopolysaccharide (125 microg/kg). Treatment with 15d-prostaglandin J(2) did not ameliorate rather enhanced at a dose of 1 mg/kg the neutrophilic lung inflammation and pulmonary edema by lipopolysaccharide. The enhancement was concomitant with the increased lung expression of interleukin-1 beta, macrophage inflammatory protein-1 alpha, and macrophage chemoattractant protein-1. 15d-prostaglandin J(2) increased the nuclear protein expression of peroxisome proliferator-activated receptor (PPAR)-gamma and inhibited the nuclear localization of nuclear factor-kappa B related to lipopolysaccharide. 15d-prostaglandin J(2) increased the phosphorylation of c-Jun in the presence or absence of lipopolysaccharide. Our data suggest that 15d-prostaglandin J(2) may not be useful but potentially harmful for the therapeutic option of acute lung injury.     

木犀草素对脂多糖诱导下小鼠急性肺损伤的保护作用及其机制研究

目的探讨木犀草素(luteolin)对脂多糖(1ipopolysaccharid,LPS)诱导的小鼠急性肺损伤的保护作用,以及可能的作用机制。方法 96只小鼠随机分为正常组、模型组、木犀草素低剂量组、木犀草素中剂量组、木犀草素高剂量组及地塞米松组,每组8只。以小鼠气道穿刺滴入LPS制备小鼠ALI模型,呼吸机检测气道吸气阻力(Ri)、气道呼气阻力(Re)和动态肺顺应性(Cdyn)的变化,ELISA法测定肺泡灌洗液(BALF)中IL-1β、IL-6和TNF-α的浓度,制作HE病理切片以及Western blot法检测肺组织中NF-κB p65、IκB-α和PIκB-α的表达情况。结果木犀草素能明显抑制Ri、Re增长和Cdyn降低,抑制BALF中IL-1β、IL-6、TNF-α的释放(P<0.05),减轻了肺部病变,抑制了NF-κB p65和PIκB-α的活化。结论木犀草素对LPS诱导的小鼠急性肺损伤具有保护作用,其作用机制与抑制NF-κB信号传导通路表达有关。     

白藜芦醇对脂多糖诱导小鼠急性肺损伤的保护作用

目的研究白藜芦醇对脂多糖(LPS)致小鼠急性肺损伤(ALI)的保护作用,探讨其可能的作用机制。方法以小鼠气道滴注LPS制备急性肺损伤模型,检测气道吸气阻力(Ri)、气道呼气阻力(Re)和动态肺顺应性(Cdyn)的变化,测定支气管肺泡灌洗液(BALF)中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的含量,检测肺湿/干比值和毛细血管通透性,观察组织病理学变化。结果白藜芦醇能明显抑制Ri、Re增长和Cdyn降低,降低BALF中IL-1βI、L-6、TNF-α的含量,降低肺湿/干比值和渗透性,减轻肺组织病理学的损伤。结论白藜芦醇对LPS诱导的ALI具有保护作用,作用机制可能与抑制炎症因子的合成与释放有关。     

硫化氢对大鼠内毒素性急性肺损伤的影响

目的观察硫化氢(H2S)对脂多糖(LPS)所致大鼠内毒素性急性肺损伤(ALI)的影响,探讨其对肺脏的作用机制。方法♂SD大鼠共64只,随机分为8组,每组8只:Ⅰ:3h空白对照组;Ⅱ:LPS3h组;Ⅲ:6h空白对照组;Ⅳ:LPS6h组;Ⅴ:LPS+NaHS低剂量组;Ⅵ:LPS+NaHS中剂量组;Ⅶ:LPS+NaHS高剂量组;Ⅷ:LPS+PPG组。LPS3h和LPS6h组给予LPS,其相应空白对照组给予生理盐水,分别在3h或6h时处死大鼠;LPS+NaHS低、中、高剂量组和LPS+PPG组分别在给LPS3h时腹腔注射低、中、高剂量氢硫化钠(NaHS)或炔丙基甘氨酸(PPG),再观察3h后处死大鼠。光、电镜下观察肺组织形态学改变,检测肺系数、肺湿/干重比(W/D)、血浆中H2S含量、肺组织胱硫醚-γ-裂解酶(CSE)活性,以及肺组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性的变化。结果LPS3h和LPS6h组与相应的空白对照组比较,光、电镜下肺组织明显受损,超微结构明显改变,肺系数、肺湿/干重比和肺组织MDA含量升高,血浆中H2S的含量、肺组织CSE以及SOD、GSH-Px活性降低。LPS+NaHS低、中、高剂量组与LPS6h组比较,光、电镜下肺组织受损情况均有不同程度改善,肺系数、肺湿/干重比和肺组织MDA含量降低,血浆H2S含量、肺组织CSE以及SOD、GSH-Px活性升高。LPS+PPG组与LPS6h组比较,光、电镜下肺组织损伤无改善,肺系数、肺湿/干重比和肺组织MDA含量升高,血浆中H2S的含量、肺组织CSE和SOD活性降低,肺组织GSH-Px活性无明显变化。结论CSE/H2S体系可能参与内毒素性ALI的病理生理过程,外源性补充H2S可减轻内毒素性ALI。     

Protective effects of apocynin nitrone on acute lung injury induced by lipopolysaccharide in rats

Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. In a previous study we reported the synthesis of a series of apocynin derivatives. Although the anti-inflammatory activity of them contributes to these cytoprotective effects. However, the mechanisms and effects of improving LPS-induced ALI in vivo remain unknown, so the purpose of our investigation was designed to reveal the effect of apocynin derivatives on LPS-induced acute lung injury in rats. The present study showed that apocynin derivatives reduces overall protein levels and tumor necrosis factor α (TNF-α) level, inhibits the activation of NADPH oxidase, and increases the levels of superoxide dismutase (SOD). Especially, compound 11 significantly reduces pulmonary vascular permeability, white blood cell content and protein expressions of p67^phox and p47^phox. These results suggest that compound 11 can ameliorate ALI induced by LPS through inhibition of NADPH oxidase.     

Escin attenuates acute lung injury induced by endotoxin in mice

Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and antiedematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity.     

氨溴索联合地塞米松对脂多糖诱导的急性肺损伤大鼠肺表面活性蛋白A的影响

目的观察氨溴索和地塞米松联用对脂多糖诱导的急性肺损伤(ALI)大鼠肺表面活性蛋白A(SP-A)表达的影响。方法 SD大鼠42只,随机分成六组,每组7只。空白对照组无处理,阴性对照组自尾静脉注入生理盐水2 mL。其余四组均给予脂多糖5 mg·kg-1,在此基础上氨溴索组予氨溴索100 mg·kg-1,地塞米松组予地塞米松6 mg·kg-1,联合用药组予氨溴索60 mg·kg-1+地塞米松4 mg·kg-1。检测各组血气分析指标、肺组织湿干重比及病理学改变,采用免疫组化和RT-PCR测定各组肺组织SP-A含量及mRNA表达。结果空白对照组和阴性对照组各项指标均无显著差异(P>0.05)。与对照组比较,模型组大鼠动脉血pH值和PaO2降低,肺组织湿干重比增高,SP-A含量及其mRNA表达均下降,差异均有显著意义(P<0.05),病理损伤明显。与模型组比较,各给药组pH值和PaO2增高,肺组织湿干重比降低,SP-A含量及其mRNA表达均升高(P<0.05),病理损伤明显改善,联合用药组改善优于氨溴索组和地塞米松组(P<0.05)。结论氨溴索与地塞米松可能通过提高肺组织SP-A含量对ALI大鼠起保护作用,两药合用效果更佳。     

腺苷酸环化酶抑制剂和激动剂在脂多糖诱导的急性肺损伤中的作用

目的探讨腺苷酸环化酶抑制剂(SQ22536)和激动剂(Forskolin)在脂多糖(LPS)诱导的急性肺损伤(acute lung injury,ALI)中的作用。方法 ICR小鼠随机分为生理盐水组(N组)、模型组(L组)、地塞米松组(D组)、SQ22536组(SQ组)和Forskolin组(F组),气道内滴入LPS制备ALI模型。6 h后观察肺组织病理改变,测定肺泡灌洗液(BALF)中白细胞、中性粒细胞和白蛋白含量,检测肺组织中髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)、白介素-1β(IL~(-1)β)、白介素-6(IL-6)和c AMP含量。结果 Forskolin可明显改善肺组织病理变化,降低BALF中白细胞、中性粒细胞和蛋白含量,MPO活性和TNF-α含量明显降低,c AMP含量升高;SQ22536与M组相比差异均无显著性。结论 Forskolin对ALI的保护机制可能与升高c AMP水平、抑制中性粒细胞黏附和趋化及降低TNF-α等相关炎症因子含量有关。     

表没食子儿茶素没食子酸酯对小鼠油酸型肺损伤的保护作用

目的研究表没食子儿茶素没食子酸酯(EGCG)对油酸型小鼠肺损伤的保护作用，并探讨其作用机制。方法以油酸型小鼠为研究对象，利用光镜、电镜观察肺部形态学变化，称重法计算肺指数及湿/干重比(w/d)，应用酶联免疫吸附法(ELISA)检测血清中TNF-α含量及Western blotting法测定肺组织中p38 MAPK的磷酸化程度。结果EGCG可明显减轻油酸组小鼠肺组织病理学改变，降低肺指数及肺湿/干重比，降低血清中炎症因子TNF-α的含量，抑制肺组织中p38 MAPK的磷酸化。结论EGCG有明显的抗油酸型小鼠肺损伤的作用，其作用机制可能与抑制p38 MAPK的磷酸化，并最终导致TNF-α的合成与释放减少有关。     

多西环素减轻小鼠内毒素性急性肺损伤的作用及机制研究

目的：探讨多西环素对内毒素性急性肺损伤的影响及机制。方法：将昆明小鼠随机分为：生理盐水对照组、多西环素组、内毒素脂多糖（LPS）急性肺损伤模型组及多西环素干预组。注射LPS24h后处死动物,行支气管肺泡灌洗（BALF）,计数灌洗液中白细胞数量及测定总蛋白含量。用ELISA分别测定肺组织匀浆上清液中TNF-a、基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制剂-1（TIMP-1）的含量。同时取肺组织进行病理学观察,测定肺组织湿/干重比值。结果：多西环素显著减少LPS所致BALF中白细胞数量、总蛋白浓度和肺组织湿/干重比值（P〈0.01）。多西环素能降低肺组织匀浆上清液中TNF-a和MMP-9含量（P〈0.01）,轻度上调TIMP-1的含量。多西环素能显著减轻LPS所致肺组织出血、肺水肿及炎性细胞浸润等肺损伤改变。结论：多西环素可减轻LPS所致急性肺损伤,其机制可能与抑制TNF-α等促炎因子释放及下调MMP-9/TIMP-1比值有关。     

Protective effect of raloxifene on lipopolysaccharide and acid- induced acute lung injury in rats

Aim： To evaluate the protective effect of oral raloxifene on acute lung injury. Methods： Thirty adult, male Sprague-Dawley rats each weighing 180-210 g were used and divided into 3 groups： the raloxifene-lipopolysaccharide （LPS）-HCI group （n=10）, the LPS-raloxifene-HCl group （n=10）, and the placebo group （n=10）. All the rats were injected intraperitoneally （ip） with 5 mg/kg LPS, and raloxifene （30 mg/kg） was orally administered 1 h before and 14 h after LPS injection into the raloxifene-LPS-HCl and the LPS-raloxifene-HCl groups, respectively; the placebo group received nothing. Sixteen hours after LPS injection, all the animals were anesthetized and the femoral artery was cannulated. All the rats received a direct intratracheal （IT） injection ofHCl （pH 1.2; 0.5 mL/kg）. The mean arterial pressure （MAP） and blood gas concentrations were measured. Fifteen rats （5 in each group, respectively） underwent a micro positron emission tomography （microPET） scan of the thorax 4 h after HCI instillation. The wet/dry （W/D） weight ratio determination and histopathological examination were also performed. Results： The rats in the LPS-raloxifene-HCl group had a lower [^18F]fluorodeoxyglucose uptake compared with the rats in the placebo group （4.67±1.33 vs 9.01±1.58, respectively, P〈0.01）. The rats in the LPS-raloxifene-HCl group also had a lower histological lung injury score （8.20± 1.23 vs 12.6±0.97, respectively, P〈0.01） and W/D weight ratio （5.335±0.198 vs 5.886±0.257, respectively, P〈0.01） compared to the placebo group. The rats in this group also showed better pulmonary gas exchange and more stable mean arterial pressure （MAP） compared to the placebo group. Conclusion： Raloxifene provides a significant protective effect on acute lung injury in rats induced first by LPS ip injection and then by HCI IT instillation.     

甘氨酸对腹腔感染小鼠急性肺损伤的作用

目的 :探讨甘氨酸对腹腔感染小鼠急性肺损伤的保护作用。方法 :2 4只昆明小鼠随机分为 3组 ,每组 8只 :假手术组 ;盲肠结扎穿孔急性肺损伤组 ;甘氨酸保护组 (1.0 g/ kg)。 2 4h后测定各组动物肺系数 ,血清 TNF浓度和肺组织中丙二醛 (MDA)、髓过氧化物酶 (MPO)及还原型谷胱甘肽 (GSH)水平 ,光镜观察肺病理改变。结果 :甘氨酸可显著抑制腹腔感染小鼠急性肺损伤时的 MDA、MPO、TNF升高 ,降低肺系数 ,减轻肺组织学病变 ,但对肺 GSH无提高作用。结论 :甘氨酸对严重腹腔感染引起的急性肺损伤有防治作用。     

Effects of carbon black nanoparticles on elastase-induced emphysematous lung injury in mice

Although adverse health effects of particulate matter with a diameter of <100 nm (nanoparticles) have been proposed, biological evidence supporting their promotion of the inflammatory lung response in vivo is limited. This study investigated the impact of pulmonary exposure to carbon black nanoparticles (CBNP) on emphysematous lung injury induced by porcine pancreatic elastase (PPE) in mice. Vehicle, two sizes (14 and 56 nm) of CBNP (50 μg/body: 4 mg/kg), PPE (0.03 U/body: 1 U/kg) or PPE + CBNP was administered intratracheally; thereafter, parameters of inflammatory lung changes were evaluated at several time-points. CBNP of 14 nm significantly induced acute lung inflammation in non-elicited subjects and aggravated PPE-elicited airway neutrophilic inflammation at an early stage (day 1), which was concomitant with the enhanced lung expression of pro-inflammatory cytokines such as interleukin-1β and chemokine such as keratinocyte-derived chemoattractant. Further, 14-nm CBNP exaggerated emphysematous lung structural changes at a delayed stage (day 14). On the other hand, 56-nm CBNP induced lung inflammation but did not influence PPE-elicited pathophysiology in the lung. Taken together, CBNP at an optimal size and dose can exacerbate PPE-induced pulmonary inflammation and emphysema. This enhancement may be mediated, at least partly, via the increased local expression of pro-inflammatory molecules.