Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP)

Vietti, Giulia; Lison, Dominique; van den Brule, Sybille

doi:10.1186/s12989-016-0123-y

Particle and Fibre Toxicology

Table 4 In vitro CNT activities on fibroblast, macrophage or epithelial cell

From: Mechanisms of lung fibrosis induced by carbon nanotubes: towards an Adverse Outcome Pathway (AOP)

Cell		CNT					Concentrations	Effects	Mechanisms	References
Type	Name	Type	Source	Length (μm)	Diameter (nm)	Other
Fibroblast	CRL1490	AP MWCNT D				BSA + DPPC		P
		AP MWCNT ND				/		/
		PD MWCNT D	CT	10–30	20–30	BSA + DPPC	5 μg/ml	P	nd	[30]
		PD MWCNT ND	CT	10–30	20–30	/	5 μg/ml	/	nd	[30]
		COOH MWCNT D				BSA + DPPC		/
		COOH MWCNT ND				/		/
Fibroblast	MLg, HFL-1,	MWCNT NM400	N	0.7–3	5–35		7.5–30 μg/cm²	P
	BALB-3 T3,	MWCNT NM402	A	0.7–4	6–20		(12–48 μg/ml)	P	nd	[23]
	PMF	MWCNT NM400c	N	0.1–0.5	18–35			/
		MWCNTg 2400	PIH	0.7	20–50			/
Fibroblast	MLg	MWCNT NM400	N	0.7–3	5–35		7.5–15 μg/cm²	P	KR, End, Erk 1/2
		MWCNT long	CT	10–30	11–59		(12–24 μg/ml)	P	Erk 1/2	[34]
		MWCNT short	CT	0.5–2	10–47			/
		MWCNT thick	CT	10–30	15–74			/
Fibroblast	NIH-3 T3	MWCNT	NP	20–50	50		15–60 μg/ml	P, C, D	Smad	[24]
Fibroblast	CRL1490	SWCNT	CNI				0.02–0.24 μg/cm²	P, C, MMP-9	nd	[22]
Fibroblast	CRL1490	SWCNT	CNI				(0.03–0.4 μg/ml)	P, C, MMP-9	nd	[22]
Fibroblast	CRL1490	SD SWCNT	CNI	0.1–1	0.8–1.2	SD	0.02 μg/cm²	C	nd	[29]
Fibroblast	CRL1490	AD SWCNT	CNI	0.1–1	0.8–1.2	AD	(0.03 μg/ml)	C	nd	[29]
Fibroblast	CRL1490	SWCNT	CNI	0.1–1	0.8–1.2		5–25 μg/ml	P, C, TGF-β, VEGF	ROS, p38	[14]
Fibroblast	NHLF	Short SWCNT	CT	1	11		0.02–0.2 μg/cm²	C, TGF-β	ROS	[31]
Fibroblast	NHLF	Long SWCNT		13	11		(0.03–0.4 μg/ml)	C, TGF-β	ROS	[31]
Fibroblast	WI38-VA13	MWCNT	SA	2.5–20	6–13		1–20 μg/ml	cyt, TGF-β, PDGF	ROS	[13]
Fibroblast	L929	MWCNT	SA		5.5		10–300 μg/ml	cyt	ROS	[32]
Macrophage	THP-1	SWCNT	NI	1–5	0.8–1.2		50 μg/ml	IL-1β	IFM, ROS, End	[54]
Macrophage	THP-1	MWCNT	CT	10–30	20–30		50 μg/ml	IL-1β	IFM, ROS, End	[54]
Macrophage	THP-1	SWCNT BSA-AP-Hipco	NI	1000–5000	0.7–1.1	BSA coated	50–100 μg/ml	IL-1β	IFM	[47]
		SWCNT BSA-PD-Hipco		500–1500	0.7–1.1	BSA coated		IL-1β	IFM
		SWCNT PF108-Hipco		500–1500	0.7-1.1	PF108 coated		/
		SWCNT BSA-AP-Arc		100–1000	1.2–2	BSA coated		IL-1β	nd
		SWCNT BSA-PD-Arc		100–1000	1.2–2	BSA coated		IL-1β	nd
		SWCNT PF108-Arc		100–1000	1.2–2	PF108 coated		/
		SWCNT BSA-PD-SG65		450–2000	0.7–1	BSA coated		IL-1β	nd
		SWCNT PF108-SG65		450-2000	0.7–1	PF108 coated		/
Macrophage	THP-1	MWCNT	BNR		67		2–10 μg/ml	IL-1β	IFM, ROCK, End	[46]
Macrophage	THP-1	AP MWCNT D	CT			BSA + DPPC	10–100 μg/ml	IL-1β	nd
		AP MWCNT ND	CT			/
		PD MWCNT D	From AP	10–30	20–30	BSA + DPPC				[36]
		PD MWCNT ND	From AP	10–30	20–30	/
		COOH MWCNT D	From AP			BSA + DPPC
		COOH MWCNT ND	From AP			/
Macrophage	PM, PBMC	short MWCNT	BMS	1–10	5–20			/
		long tangled MWCNT	CT	10–50	8–15		10–100 μg/ml	/		[43]
		long needle-like MWCNT	MC	13	>50		10–100 μg/ml	IL-1β, IL-α	IFM, ROS, Src, Syc,
		(Mitsui MWCNT-7)							P2X7 R
Macrophage	PAM	raw MWCNT				/		IL-1β, IL-18	IFM
	THP-1	pure MWCNT				PD		IL-1β, IL-18	IFM
		raw MWCNT COOH	NAM			COOH F	25–100 μg/ml	/		[42]
		pure MWCNT COOH				COOH F - PD		/
Macrophage	PHM	DWCNT	PIH	0.1–100	1.2–3.2		25 μg/ml	IL-1β, IL-18	IFM, End, K efflux	[44]
Macrophage	RAW 264.7	MWCNT	SA	2.5–20	6–13		2–20 μg/ml	IL-1β, TNF-α, IL-6, IL-10, MCP-1	NF-kB	[13]
Macrophage	THP-1, PBMC	MWCNT	HMS	0.5–40	10–30	Uncoated	10–100 μg/ml	IL-1β, TNF-α,	nd	[50]
						ALD-coated		IL-6, OPN
						ALD-coated		IL-1β
Macrophage	PAM	Short MWCNT	Nth	1.1	30		10 μg/ml	/		[58]
Macrophage	PAM	Long MWCNT		20	28			IL-6, IL-8	ROS	[58]
Macrophage	THP-1	MWCNT AP	CT	0.57		F		IL-1β, TGF-β, PDGF
		MWCNT NH2	From AP	0.45		F		IL-1β, TGF-β, PDGF
		MWCNT sw-NH2	From AP	0.58		F		IL-1β, TGF-β, PDGF
		MWCNT PEI	From AP	0.33		F	60 μg/ml	IL-1β, TGF-β, PDGF	for IL-1β: IFM, End	[45]
		MWCNT PEG	From AP	0.27		F		IL-1β, TGF-β
		MWCNT cc-PEI	From AP	0.38		F		/
		MWCNT COOH	From AP					/
Macrophage	RAW 264.7	SWCNT	CNI		1–4		100 μg/ml	TGF-β	nd	[38]
Macrophage	RAW 264.7	Short MWCNT	NP	0.5–2	50		15 μg/ml	/		[15]
Macrophage	RAW 264.7	Long MWCNT		20–50	50			TGF-β, TNF-α	nd
Macrophage	NR8383	MWCNT	HMS	0.3–50	10–30		10 μg/cm²	PDGF	nd	[51]
Macrophage	NR8383	MWCNT	HMS	0.3–50	10–30		(16 μg/ml)	PDGF	nd	[51]
Epithelial cell	A549	Short MWCNT	SN	0.35–0.7	10–20		1–16 μg/cm²	/		[65]
Epithelial cell	A549	Long MWCNT		5–15	10–20		(1.6–25.6 μg/ml)	EMT	TGF-β/Smad	[65]
Epithelial cell	RLE-6TN	MWCNT	NP	20–50	50		30 μg/ml	EMT	TGF-β/Smad	[24]
Epithelial cell	HBE	MWCNT	HMS	0.5–40	10–30		1.5–24 μg/ml	IL-1β, IL-18	IFM, ROS	[16]
Epithelial cell	HBE	MWCNT	HMS	0.5–40	10–30		1.5–24 μg/ml	IL-8	IFM, ROS	[16]
Epithelial cell	BEAS-2B	MWCNT	BNR		67		1–10 μg/ml	IL-6, IL-8, MIF	NF-kB, p38,	[71]
Epithelial cell	BEAS-2B	MWCNT	BNR		67		1–10 μg/ml	IL-6, IL-8, MIF	ERK 1/2, HSP27	[71]
Epithelial cell	TT1, ATII	MWCNT 0.6 μm	Nth	1.1	30			IL-6, IL-8, MCP-1
		MWCNT 3 μm		4.3	33		1–50 μg/ml	IL-8, MCP-1	JNK, p38, ERK 1/2	[67]
		MWCNT 20 μm		20	28			MCP-1
Epithelial cell	BEAS-2B	SWCNT BSA-AP-Hipco	NI	1000–5000	0.7–1.1	BSA coated		TGF-β
		SWCNT BSA-PD-Hipco		500–1500	0.7–1.1	BSA coated		TGF-β
		SWCNT PF108-Hipco		500–1500	0.7–1.1	PF108 coated		/
		SWCNT BSA-AP-Arc		100–1000	1.2–2	BSA coated	100 μg/ml	TGF-β	nd	[47]
		SWCNT BSA-PD-Arc		100–1000	1.2–2	BSA coated	100 μg/ml	TGF-β	nd	[47]
		SWCNT PF108-Arc		100–1000	1.2–2	PF108 coated		TGF-β
		SWCNT BSA-PD-SG65		450–2000	0.7–1	BSA coated		TGF-β
		SWCNT PF108-SG65		450–2000	0.7–1	PF108 coated		/
Epithelial cell	BEAS-2B	AP MWCNT D	CT	10–30	20–30	BSA + DPPC	10–100 μg/ml	TGF-β		[36]
		AP MWCNT ND	CT			/		/
		PD MWCNT D	From AP			BSA + DPPC		TGF-β
		PD MWCNT ND	From AP			/		/	nd
		COOH MWCNT D	From AP			BSA + DPPC		Few TGF-β	nd
		COOH MWCNT ND	From AP			/		Few TGF-β
Epithelial cell	BEAS-2B	MWCNT	SA	2.5–20	6–13		2–200 μg/ml	TGF-β, PDGF	ROS	[13]

nd: not determined. Cell name: A549: human lung adenocarcinoma alveolar epithelial cell line; ATII: primary human alveolar type-II epithelial cells; BALB-3 T3: mouse embryonic fibroblast cell line; BEAS-2B: human bronchial epithelial cell line; CRL1490: human lung fibroblast cell line; HBE: primary human bronchial epithelial cells; HFL-1: human lung fibroblast cell line; L929: mouse fibroblast cell line; MLg: mouse lung fibroblast cell line; NHLF: normal human lung fibroblast cell line; NIH-3 T3: mouse embryonic fibroblast cell line; NR8383: rat alveolar macrophage cell line; PAM: primary alveolar macrophages; PBMC: peripherial blood mononuclear cells; PHM: primary human monocytes; PMF: primary mouse fibroblasts; RAW 264.7: mouse leukemic monocyte macrophage cell line; RLE-6TN: rat alveolar type II epithelial cell line; THP-1: human leukemia monocytic cell line; TT1: transformed human alveolar type-I-like epithelial cells; WI38-VA13: human normal lung fibroblast cell line immortalized with SV40. CNT type: AP: as prepared; COOH: carboxyl; NH2: amino; PD: purified. Source: A: Arkema (France); BMS: Bayer Material Science (Leverkusen, Germany); BNR: Bussan Nanotech Research (Ibaraki, Japan); CNI: Carbon Nanotechnologies Inc. (Houston, TX); CT: Cheap Tubes (Brattlebore, VT); HMS : Helix Materials Solution (Richardson, TX); MC: Mitsui & Company (Tokio, Japan); N: Nanocyl (Sambreville, Belgium); NAM: Nanostructured & Amorphous Materials Inc. (Houston, TX); NI: NanoIntegris (Skokie, IL); NP: Nanotech Port (Chengdu, China); Nth: Nanothinx (Rio Patras, Greece); PIH: produced in house; SA: Sigma-Aldrich (Lyon, France); SN: Shenzhen Nanoharbor (Shenzhen, China). Other: AD: acetone/sonication dispersed; BSA: bovine serum albumin; cc-PEI: carboxyl converted PEI; D: dispersed; DPPC: dipalmitoylphosphatidylcholine; F: functionalized; ND: no dispersed; PEG: polyethylene glycol; PEI: polyethyleneimine; PF108: Pluronic F108; SD: survanta dispersed; swNH2: sidewall amine. Effects: C: collagen; cyt: cytotoxic; D: differentiation of fibroblasts into myofibroblasts; EMT: epithelial mesenchymal transition; IL: interleukin; MCP: monocyte chemoattractant protein; MIF: migration inhibitory factor; MMP-9: matrix metallopeptidase 9; OPN: osteopontin; P: proliferation; PDGF: platelet derived growth factor; TGF: transforming growth factor; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor. Mechanisms: End: endocytosis; ERK 1/2: extracellular signal-regulated kinase; HSP27: heat shock protein 27; IFM: inflammasome; JNK: c-Jun N-terminal kinase; K: potassium; KR: kinase receptor; NF-kB: nuclear factor-kappa B; ROCK: Rho-kinases; ROS: reactive oxygen species

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