Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway

Mizuno, Keita; Fukami, Tatsuki; Toyoda, Yasuyuki; Nakajima, Miki; Yokoi, Tsuyoshi

doi:10.1016/j.lfs.2010.08.010

Cited by 20 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Samples of uninfected macrophages (C; control) were collected 6 h post-infection (pi) while infected macrophages were collected at three time points (T1-T3) corresponding to 2, 6 and 24 h pi with the objective of a) elucidation of the general macrophage response triggered by B. pertussis (6 h pi) and b) monitoring the time-dependent changes in gene expression profiles resulting from the hostpathogen interaction within the early phase of infection (T2 versus T1) and within the late phase of infection (T3 versus T2). We did not use the uninfected controls for T1 and T3 time points as the changes in gene expression profiles of THP-1 macrophages incubated for 24 h in RPMI medium are not substantial [26] and in particular, expression of several cytokines and chemokines remains unchanged during 24 h incubation in RPMI medium [27,28]. RNA-seq analysis of samples from infected cells and uninfected control yielded on average 16 million reads which were mapped to human and B. pertussis genomes ( Fig S1).…”

Section: Resultsmentioning

confidence: 99%

Transcriptional profiling of human macrophages during infection withBordetella pertussis

et al. 2020

View full text Add to dashboard Cite

Bordetella pertussis, a strictly human re-emerging pathogen and the causative agent of whooping cough, exploits a broad variety of virulence factors to establish efficient infection. Here, we used RNA sequencing to analyse the changes in gene expression profiles of human THP-1 macrophages resulting from B. pertussis infection. In parallel, we attempted to determine the changes in intracellular B. pertussisspecific transcriptomic profiles resulting from interaction with macrophages. Our analysis revealed that global gene expression profiles in THP-1 macrophages are extensively rewired 6 h post-infection. Among the highly expressed genes, we identified those encoding cytokines, chemokines, and transcription regulators involved in the induction of the M1 and M2 macrophage polarization programmes. Notably, several host genes involved in the control of apoptosis and inflammation which are known to be hijacked by intracellular bacterial pathogens were overexpressed upon infection. Furthermore, in silico analyses identified large temporal changes in expression of specific gene subsets involved in signalling and metabolic pathways. Despite limited numbers of the bacterial reads, we observed reduced expression of majority of virulence factors and upregulation of several transcriptional regulators during infection suggesting that intracellular B. pertussis cells switch from virulent to avirulent phase and actively adapt to intracellular environment, respectively.

show abstract

Section: Resultsmentioning

confidence: 99%

Transcriptional profiling of human macrophages during infection withBordetella pertussis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Therefore, we focused on the expression of these three genes in the following experiments. In our previous study (Mizuno et al ., ), we confirmed the expression levels of mRNA and protein were similar in cytokines. Thus, changes in mRNA expression were followed in the present study.…”

Section: Resultsmentioning

confidence: 97%

Allopurinol induces innate immune responses through mitogen‐activated protein kinase signaling pathways in HL‐60 cells

Nakajima

Oda

Yokoi

2015

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

Allopurinol, an inhibitor of xanthine oxidase, is a frequent cause of severe cutaneous adverse reactions (SCARs) in humans, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis. Although SCARs have been suspected to be immune-mediated, the mechanisms of allopurinol-induced SCARs remain unclear. In this study, we examined whether allopurinol has the ability to induce innate immune responses in vitro using human dendritic cell (DC)-like cell lines, including HL-60, THP-1 and K562, and a human keratinocyte cell line, HaCaT. In this study, we demonstrate that treatment of HL-60 cells with allopurinol significantly increased the mRNA expression levels of interleukin-8, monocyte chemotactic protein-1 and tumor necrosis factor α in a time- and concentration-dependent manner. Furthermore, allopurinol induced the phosphorylation of mitogen-activated protein kinases (MAPK), such as c-Jun N-terminal kinase and extracellular signal-regulated kinase, which regulate cytokine production in DC. In addition, allopurinol-induced increases in cytokine expression were inhibited by co-treatment with the MAPK inhibitors. Collectively, these results suggest that allopurinol has the ability to induce innate immune responses in a DC-like cell line through activation of the MAPK signaling pathways. These results indicate that innate immune responses induced by allopurinol might be involved in the development of allopurinol-induced SCARs. Copyright © 2015 John Wiley & Sons, Ltd.

show abstract

“…There is limited data from the various case reports on an underlying inflammatory mechanism but it has been demonstrated that treatment of monocytes with terbinafine results in the release of the proinflammatory cytokines IL-8 and TNF-alpha. 30 Metabolism of terbinafine is complex involving several different cytochromes P450. 31 However, there was no evidence from the GWAS for a role for either CYP genes or innate immunity genes in the terbinafine DILI cases studied.…”

Section: Discussionmentioning

confidence: 99%

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study

et al. 2017

View full text Add to dashboard Cite

BACKGROUND & AIMS We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS We performed a GWAS of 862 persons with DILI and 10588 population-matched controls. The first set of cases was recruited prior to May 2009 in Europe (n=137) or the USA (n=274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the USA and South America. For the GWAS, we included only cases of European ancestry associated with a particular drug (but not flucloxacillin or amoxicillin-clavulanate). We used DNA samples from all subjects to analyze human leukocyte antigen (HLA) genes and single nucleotide polymorphisms (SNPs). After the discovery analysis was concluded, we validated our findings using data from 283 European patients with diagnosis of DILI associated with various drugs. RESULTS We associated DILI with rs114577328 (a proxy for A*33:01 a HLA class I allele; odds ratio [OR], 2.7; 95% CI, 1.9–3.8; P=2.4×10−8) and with rs72631567 on chromosome 2 (OR, 2.0; 95% CI, 1.6–2.5; P=9.7×10−9). The association with A*33:01 was mediated by large effects for terbinafine-, fenofibrate-, and ticlopidine-related DILI. The variant on chromosome 2 was associated with DILI from a variety of drugs. Further phenotypic analysis indicated that the association between DILI and A*33:01 was significant, genome wide, for cholestatic and mixed DILI, but not for hepatocellular DILI; the polymorphism on chromosome 2 associated with cholestatic and mixed DILI as well as hepatocellular DILI. We identified an association between rs28521457 (within the LRBA gene) and only hepatocellular DILI (OR, 2.1; 95% CI, 1.6–2.7; P=4.8×10−9). We did not associate any specific drug classes with genetic polymorphisms, except for statin-associated DILI, which was associated with rs116561224 on chromosome 18 (OR=5.4; 95% CI, 3.0–9.5; P=7.1×10−9). We validated the association between A*33:01 terbinafine- and sertraline-induced DILI. We could not validate the association between DILI and rs72631567, rs28521457, or rs116561224. CONCLUSIONS In a GWAS of persons of European descent with DILI, we associated HLA-A*33:01 with DILI due to terbinafine and possibly fenofibrate and ticlopidine. We identified polymorphisms that appear to be associated with DILI from statins, as well as 2 non–drug-specific risk factors.

show abstract

Terbinafine stimulates the pro-inflammatory responses in human monocytic THP-1 cells through an ERK signaling pathway

Cited by 20 publications

References 30 publications

Transcriptional profiling of human macrophages during infection withBordetella pertussis

Transcriptional profiling of human macrophages during infection withBordetella pertussis

Allopurinol induces innate immune responses through mitogen‐activated protein kinase signaling pathways in HL‐60 cells

Association of Liver Injury From Specific Drugs, or Groups of Drugs, With Polymorphisms in HLA and Other Genes in a Genome-Wide Association Study

Contact Info

Product

Resources

About