Table 3 Review of reported effects on inflammatory cascade in varying skin models upon exposure to PM
Model | PM type | Dose and application | Exposure time | Main findings | Ref. |
|---|---|---|---|---|---|
Ex vivo human skin | SRM® 1649b | 2 mg/cm2, topical | 24 h | - Increased MMP-1 protein expression. | [119] |
Mice, BALB/c | SRM® 1649b | 100 μg/m2, topical | 24 h repetitive exposure, 5 d total | - Increased COX2 protein expression. | [122] |
SRM® 1649b | 100 μg/cm2, topical | 24 h repetitive exposure, 5 d total | - Increased epidermal thickness. - Neutrophil infiltration. - Increased COX2 protein expression. | [179] | |
Mice, BALB/c with disrupted barrier | PM ≤1 μm from Seoul, Korea | 8 μg/cm2, topical | 6 h and 2 w repetitive exposures, 10 times in total | - Increased epidermal thickness in both skin types. - Neutrophil infiltration. - Increased mRNA expression of IL-8 functional homologs (KC, MIP2, LIX). - Increased mRNA expression MMP13. | [121] |
Mice, NC/Nga, AE model | The soluble phase of DEP. | 1 mg/time, topical | Repetitive exposure, every 1, 3, or 9 weeks in total | - Increased AE lesion formation. - Increased total IgE levels. | [226] |
Mice, HR-1 | SRM® 1650b | 100 μg/mL, topical | 7 d | - Increased epidermal thickness. | [124] |
SRM® 1650b | 100 μg/mL, topical | 7 d | - Increased epidermal thickness. | [168] | |
SRM® 1650b | 100 μg/mL, topical | 7 d | - Increased IL-1β and IL-6 protein expression. - Increased TLR5 protein expression. - Increased MyD88 protein expression. - Increased phosphorylation of p65. | [169] | |
HSE | SRM® 2975 | 200 μg/mL, systemic | Every 2 d, 6 d total | - Decreased IL-8, CXCL10, and ICAM1 protein secretion. | [125] |
HEE | CAPs, PM2.5 | 0.5 and 2.0 μg/cm2, topical | 24 and 48 h | - Nuclear translocation of p65. - Increased IL-1α protein secretion. - Increased COX2 protein expression. | [128] |
CRM no. 28 | 25 mg, topical | 6 and 24 h | - Upregulated mRNA expression of IL1A, IL1B, IL6, CXCL8, CCL20, MMP1, MMP3, MMP9, MMP12, and ICAM1 after 6 h. - Downregulated expression of tissue inhibitors of MMPs (2–4) after 6 h. - Induced IL-8 and MMP-1 protein secretion after 24 h. | [129] | |
PM0.3–2.5 from Benin, West-Africa | 15 and 30 μg/cm2, topical | 24 h | - Increased IL-1α and IL-8 protein secretion. - Increased MMP-1 and MMP-3 protein expression. | [133] | |
PM2.5 from Seoul, Korea | 50 μg/mL, topical | 24 h | - Increased MMP-1 protein expression. | [132] | |
SRM® 1648a | 2.2, 8.9, and 17.9 μg/cm2, topical | 24 and 48 h | - Increased IL-1α protein secretion. | [131] | |
NHDF | SRM® 1649b | 100–400 μg/mL, systemic | 24 h | - Phosphorylation of ERK and JNK. - Increased MMP1 mRNA and protein expression. | [172] |
Diesel PM | 30 and 60 μg/mL, systemic | 24 h | - Increased MMP3 and MMP9 mRNA expression. | [138] | |
SRM® 1649b | 50 μg/mL, systemic | 24 h | - Increased MMP1 mRNA expression. | [119] | |
SRM® 2787 | 30 μg/cm2, systemic | 24 h | - Increased IL-6 and IL-8 protein secretion. - Increased MMP-1 and decreased procollagen and TGF-β protein secretion. - Increased IL1B, IL6, CXCL8, and IL33 mRNA expression. - Increased MMP1 and MMP3 and decreased TGFB, collagen type I alpha 1 chain, collagen type I alpha 2 chain, and elastin mRNA expression. | [135] | |
ERM-CZ100 | 200 μg/mL, systemic | 24 h | - Increased MMP-1, −2,-8, −9, −13 protein expression. - Nuclear translocation of p65. - Phosphorylation of ERK, JNK, and p38. | [136] | |
The pre-conditioned medium of HaCaT treated with CRM no. 28 | 125 μg/mL, systemic | 30 m, 48 h post-incubation | - Increased PGE2, TNF-α, IL-1β, and IL-6 protein secretion. - Increased COX2 protein expression. - Nuclear translocation of p65. - Phosphorylation of p38, ERK, and JNK. - Increased MMP-1 and MMP-2 protein expression. | [137] | |
Diesel PM | 30 and 60 μg/mL, systemic | 6 h | - Increased MMP2 and MMP9 mRNA expression. | [227] | |
NHDF and HaCaT co-culture | SRM® 1648a and SRM® 1649b | 50 μg/cm2, systemic | 24 h | - Phosphorylation of p38. - Increased IL1A, IL1B, IL6, and CXCL8 mRNA expression and protein secretion (HaCaT). - No changes in TNF mRNA expression and protein secretion (HaCaT). - Increased MMP1 and COX2 mRNA expression (NHDF). | [178] |
NHEK | PM2.5 from Xi’an, China | 50 μg/mL, systemic | 24 h | - Top upregulated genes from transcriptomics analysis are CXCL1, IL1A, and IL1B. | [134] |
Diesel PM | 30 and 60 μg/mL, systemic | 24 h | - Increased IL1A, IL6, CXCL8, and TNF mRNA expression and protein secretion. | [138] | |
ERM-CZ120 | 3, 10, 30 and 100 μg/mL, systemic | 24 and 48 h | - Increased IL1B, IL6, CXCL8, and TNF mRNA expression after 24 h. - Increased IL-1β, IL-6, IL-8, and TNF-α protein secretion after 48 h. - Increased MMP1 mRNA expression and protein secretion after 24 h. | [173] | |
SRM® 1650b | Unknown | 24 h | - Increased IL-1β and IL6 protein secretion. - Increased IL-6 protein expression. | [169] | |
PM ≤1 μm from Seoul, Korea | 40 μg/cm2, systemic | 24 h | - Increased CXCL8 mRNA expression and protein secretion. - Increased MMP1 mRNA expression and protein secretion. | [121] | |
SRM® 2786 | 1 mg/mL, systemic | 6 h | - RNA-Seq analysis: Upregulation of IL1B, IL36G, CXCL3, CXCL8, and IL1R2. Downregulation of MMP3 and MMP28. | [141] | |
SRM® 1649b | 50 μg/cm2, systemic | 24 h | - Increased COX2 protein expression. | [181] | |
SRM® 1649b | 100 μg/mL, systemic | 24 and 48 h | - Increased IL-8 protein secretion. | [228] | |
Diesel PM | 20 μg/mL, systemic | 48 h | - Increased IL-1β and IL-8 protein secretion. | [229] | |
Diesel PM | 30 and 60 μg/mL, systemic | 6 h | - Increased IL1A, IL6, CXCL8, and TNF mRNA expression. | [227] | |
Asian dust storm particles from Seoul, Korea | 25 μg/mL, systemic | 24 h | - Increased IL6, CXCL8, and CSF2 mRNA expression. - No changes in IL1B, IFNG, and IL18 mRNA expression. | [139] | |
PM2.5 from Seoul, Korea | 25 μg/mL, systemic | 24 h | - Top upregulated genes from transcriptomics analysis are IL1B, IL36G, IL1A, IL1R2, PTGS2, IRAK2, MMP1, MMP9, and MMP10. - Downregulated gene is CXCL14. - Induced IL-1α protein secretion. - Phosphorylation of p65 and p38. | [132] | |
HaCaT | CRM no. 28 | 125 μg/mL, systemic | 30 m, 48 h post-incubation | - Increased PGE2, TNF-α, IL-1β, and IL6 protein secretion. - Increased COX2 protein expression. - Nuclear translocation of p65. - Phosphorylation of p38, ERK, and JNK. - Increased MMP-1 and MMP-2 protein expression. | [137] |
PM2.5 from Shanghai, China | 10–100 μg/mL, systemic | 24 h | - No changes in CSF2 protein secretion. - Increased TSLP, TNF-α, IL-1α, and IL-8 protein secretion. | [144] | |
SRM® 1648a | 50–200 ppm, systemic | 24 and 48 h | - Increased TRPV1 mRNA and protein expression (via p38/MAPK and NF-κB pathway). - Increased IL-1β, IL-8, and TNF-α protein secretion. | [130] | |
SRM® 1648a and SRM® 1649b | 50 μg/cm2, systemic | 24 h | - Induced phosphorylation of p-38. | [178] | |
SRM® 1649b | 50 μg/cm2, systemic | 6 and 24 h | - Increased phosphorylation of ERK, p38, JNK, and Akt after 6 h. - Increased COX2, ICAM1, cPLA2, and PGE2 protein expression after 24 h. - Increased MMP-9 protein expression after 24 h. | [143] | |
SRM® 1649b | 50 μg/cm2, systemic | 2 and 6 h | - Increased COX2 and MMP-9 protein expression. - Phosphorylation of ERK, JNK, and p38. | [142] | |
SRM® 1649b | 25 and 50 μg/cm2, systemic | 4 and 24 h | - Increased COX2 protein expression. - Increased PGE2 and IL-6 protein secretion. - No changes in IL-24, IL-1β, and TNF-α protein secretion. | [122] | |
SRM® 1649b | 25–100 μg/cm2, systemic | 4 and 24 h | - Increased COX2 protein (24 h) and mRNA (6 h) expression. - Increased PGE2 protein secretion after 24 h. - Nuclear translocation p65 after 4 h. - Phosphorylation of ERK, JNK, and p38 after 4 h. | [179] | |
SRM® 1649b | 25 μg/mL, systemic | 2 and 24 h | - Increased IL-6, IL-1β, and IL-1α protein secretion, and mRNA expression. - Phosphorylation of p38 and AP-1. | [180] | |
SRM® 1649b | 50 μg/mL, systemic | UK | - Increased protein expression of COX2, PLA2, ICAM1, and MMP-9. - Phosphorylation of ERK, p38, and JNK. | [230] | |
SRM® 1649b | 50 μg/cm2, systemic | 6 and 24 h | - Increased COX2 protein (24 h) and mRNA (6 h) expression. - Increased PGE2 protein secretion. - Phosphorylation of p38, ERK, JNK, and p65. | [181] | |
SRM® 1649b | 100–400 μg/mL, systemic | 24 h | - Phosphorylation of ERK and JNK. - Increased MMP1 mRNA and protein expression. | [172] | |
SRM® 1650b | Unknown | 1 h | - Binding of PM to TLR5. | [169] | |
SRM® 1650b | 50 μg/mL, systemic | 24 h | - Induced phosphorylation of ERK, p38, and JNK. | [182] | |
SRM® 1650b | Unknown | 3 h | - Increased IL-1β, IL-6, IL-8, IL-16, and TGF-β2 protein secretion. - Increased IL6 mRNA expression. | [169] | |
SRM® 1650b | Unknown | 24–72 h | - Increased IL-1β, IL-6, IL-8, IL-16, and TGF-β2 protein secretion. - Increased IL-6 protein expression (time-dependent increase). - Increased IL6 mRNA expression. - Increased TLR5 protein and mRNA expression. - Increased MyD88 protein expression. - Nuclear translocation of p65. - NOX4-TLR5 interaction. | [169] | |
SRM® 1650b | 50 μg/mL, systemic | 24 h | - Phosphorylation of ERK, JNK, and p38. | [168] | |
SRM® 1650b | 50 μg/mL, systemic | 30 m, 1 h, and 24 h | - Increased MMP-1 protein activity, expression, and mRNA expression. - Increased MMP-2 and MMP-9 protein expression. - Activation of the MAPK pathway. - AP-1 binding to MMP-1 promotor. | [185] | |
SRM® 2975 | 100 and 200 μg/mL, systemic | 30 m and 24 h | - Decreased IL-8 and CXCL10 protein secretion after 24 h. - Phosphorylation of p38, ERK, and JNK after 30 min. | [125] | |
CAPs, PM2.5 | 5–25 μg/mL, systemic | 1, 3, 6 and 24 h | - Nuclear translocation of p65. - Increased IL-1α protein secretion. | [145] | |
CRM no. 28 | 125 μg/mL, systemic | 30 m, 24 h post-incubation | - Nuclear translocation of p65. - Phosphorylation of p38, ERK, and JNK. - Increased PGE2, TNF-α, and IL-6 protein secretion. - Increased COX2 protein expression. | [137] | |
CRM no. 28 | 125 μg/mL, systemic | 30 m, 24 h post-incubation | - Nuclear translocation of p65. - Phosphorylation of p38. - Increased COX2 protein expression. - Increased PGE2, IL-6, TNF-α, and IL-1β protein secretion. | [231] | |
ERM-CZ100 and ERM-CZ120 | 100 μg/mL, systemic | 24 h | - Increased IL-1β, PGE2, and IL-6 protein secretion. - Increased COX2 protein expression. | [232] | |
ERM-CZ120 | 100–400 μg/mL, systemic | 24 and 48 h | - Increased PGE2 protein secretion. | [126] | |
HEK-001 | SRM® 1650b | Unknown | 24 h | - Increased IL-1β and IL-6 protein secretion. - Increased IL-6 protein expression. | [169] |
JB6 P+, mouse cell line | SRM® 1975 | 10–20 μg/mL, systemic | 12, 24, 36, and 48 h | - Activation of NF-κB. - No activation of AP-1. - Activation of the Akt/PI3K pathway. - Phosphorylation of ERK, not of p38 and JNK. | [233] |