Details of the Drug Combination

General Information of Drug Combination (ID: DC3P733)

• Drug Combination Name: Methylprednisolone + Hydroxychloroquine
• Indication: Thrombocytopenia; Status: Phase 3 [1]
• Component Drugs:
  Methylprednisolone (DM4BDON): Small molecular drug
  Hydroxychloroquine (DMSIVND): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Methylprednisolone

Disease Entry	ICD 11	Status	REF
Acute adrenal insufficiency	N.A.	Approved	[2]
Acute asthma	CA23	Approved	[2]
Addison disease	5A74.0	Approved	[2]
Allergic rhinitis	CA08.0	Approved	[2]
Angioedema	4A00.15	Approved	[2]
Aspiration pneumonitis	N.A.	Approved	[2]
Autoimmune haemolytic anaemia	3A20	Approved	[2]
Bursitis	N.A.	Approved	[2]
Cerebral edema	8D60.1	Approved	[2]
Chronic graft versus host disease	N.A.	Approved	[2]
Congenital adrenal hyperplasia	5A71.01	Approved	[2]
Crohn disease	DD70	Approved	[2]
Dermatitis herpetiformis	EB44	Approved	[2]
Diamond-Blackfan anemia	N.A.	Approved	[2]
Disorder of orbital region	N.A.	Approved	[2]
Epicondylitis	N.A.	Approved	[2]
Erythema multiforme	N.A.	Approved	[2]
Exanthem	N.A.	Approved	[2]
Fever	MG26	Approved	[2]
Granuloma annulare	N.A.	Approved	[2]
Inflammatory bowel disease	DD72	Approved	[2]
Ischemia-reperfusion injury	DB98.B	Approved	[2]
Leukemia	N.A.	Approved	[2]
Lupus nephritis	4A40.0Y	Approved	[2]
Microscopic polyangiitis	N.A.	Approved	[2]
Miliary tuberculosis	N.A.	Approved	[2]
Multiple sclerosis	8A40	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Myeloproliferative neoplasm	2A20	Approved	[2]
Pneumocystis pneumonia	CA40.20	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Psoriasis	EA90	Approved	[2]
Psoriatic arthritis	FA21	Approved	[2]
Rheumatic heart disease	N.A.	Approved	[2]
Rheumatoid arthritis	FA20	Approved	[3]
Sarcoidosis	4B20.5	Approved	[2]
Seasonal allergic rhinitis	CA08.01	Approved	[2]
Serum sickness	N.A.	Approved	[2]
Severe asthma	CA23	Approved	[2]
Skin disease	EA00-EM0Z	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Systemic lupus erythematosus	4A40.0	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]
Acquired thrombocytopenia	N.A.	Investigative	[2]
Asthma	CA23	Investigative	[2]
Beta-thalassemia major	N.A.	Investigative	[2]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]
Follicular lymphoma	2A80	Investigative	[2]
Perennial allergic rhinitis	CA08.03	Investigative	[2]
Spinal cord injury	ND51.2	Investigative	[5]
Synovitis	N.A.	Investigative	[2]
Trichinellosis	N.A.	Investigative	[2]

Methylprednisolone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucocorticoid receptor (NR3C1)	TTYRL6O	GCR_HUMAN	Modulator	[11]

Methylprednisolone Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Methylprednisolone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]

Methylprednisolone Interacts with 87 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Decreases Expression	[14]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[15]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Expression	[9]
CCN family member 1 (CCN1)	OTKJBEMD	CCN1_HUMAN	Increases Expression	[9]
Phospholipid phosphatase 3 (PLPP3)	OTSSF7BK	PLPP3_HUMAN	Decreases Expression	[9]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Decreases Expression	[9]
Calmegin (CLGN)	OTEWVFQV	CLGN_HUMAN	Decreases Expression	[9]
D-3-phosphoglycerate dehydrogenase (PHGDH)	OT1LMRTG	SERA_HUMAN	Decreases Expression	[9]
Receptor-interacting serine/threonine-protein kinase 2 (RIPK2)	OT0KMIYQ	RIPK2_HUMAN	Decreases Expression	[9]
Gasdermin-E (GSDME)	OT1ZWY32	GSDME_HUMAN	Decreases Expression	[9]
Toll-like receptor 2 (TLR2)	OTGO5P4R	TLR2_HUMAN	Decreases Expression	[9]
CCN family member 5 (CCN5)	OTADU8JJ	CCN5_HUMAN	Increases Expression	[9]
Antiviral innate immune response receptor RIG-I (RIGI)	OTFIIC43	RIGI_HUMAN	Decreases Expression	[9]
2'-5'-oligoadenylate synthase 1 (OAS1)	OT8ZLOCY	OAS1_HUMAN	Decreases Expression	[9]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Increases Expression	[9]
Superoxide dismutase , mitochondrial (SOD2)	OTIWXGZ9	SODM_HUMAN	Decreases Expression	[9]
Ubiquitin-like protein ISG15 (ISG15)	OT53QQ7N	ISG15_HUMAN	Decreases Expression	[9]
Thrombospondin-1 (THBS1)	OT0ECWK3	TSP1_HUMAN	Increases Expression	[9]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Decreases Expression	[9]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Decreases Expression	[9]
Steryl-sulfatase (STS)	OTXTJQPC	STS_HUMAN	Increases Expression	[9]
Neuromedin-B (NMB)	OT4NLN6H	NMB_HUMAN	Decreases Expression	[9]
Stromelysin-2 (MMP10)	OTJDWW8Q	MMP10_HUMAN	Decreases Expression	[9]
Growth-regulated alpha protein (CXCL1)	OT3WCTZV	GROA_HUMAN	Decreases Expression	[9]
Interferon alpha-inducible protein 6 (IFI6)	OTWOOAM4	IFI6_HUMAN	Decreases Expression	[9]
Interferon-induced protein with tetratricopeptide repeats 1 (IFIT1)	OTXOQDSG	IFIT1_HUMAN	Decreases Expression	[9]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[9]
Interleukin-1 receptor antagonist protein (IL1RN)	OT308CBE	IL1RA_HUMAN	Decreases Expression	[9]
C-X-C motif chemokine 2 (CXCL2)	OTEJCYMY	CXCL2_HUMAN	Decreases Expression	[9]
C-X-C motif chemokine 3 (CXCL3)	OTSL94KH	CXCL3_HUMAN	Decreases Expression	[9]
Interferon-induced GTP-binding protein Mx1 (MX1)	OT6X8G5T	MX1_HUMAN	Decreases Expression	[9]
Fibulin-1 (FBLN1)	OT5MHHOP	FBLN1_HUMAN	Increases Expression	[9]
Atypical chemokine receptor 3 (ACKR3)	OTA6GA4F	ACKR3_HUMAN	Decreases Expression	[9]
11-beta-hydroxysteroid dehydrogenase 1 (HSD11B1)	OTO7FJA9	DHI1_HUMAN	Decreases Expression	[9]
Adenosine receptor A2a (ADORA2A)	OTVRBZ0I	AA2AR_HUMAN	Decreases Expression	[9]
CCN family member 2 (CCN2)	OTC39NSU	CCN2_HUMAN	Increases Expression	[9]
Myristoylated alanine-rich C-kinase substrate (MARCKS)	OT7N056G	MARCS_HUMAN	Decreases Expression	[9]
Guanylate-binding protein 1 (GBP1)	OTUM7RPJ	GBP1_HUMAN	Decreases Expression	[9]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[9]
Macrophage metalloelastase (MMP12)	OT9Z7LHM	MMP12_HUMAN	Decreases Expression	[9]
Interferon alpha-inducible protein 27, mitochondrial (IFI27)	OTI2XGIT	IFI27_HUMAN	Decreases Expression	[9]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Decreases Expression	[9]
Regulator of G-protein signaling 4 (RGS4)	OTG94HHL	RGS4_HUMAN	Decreases Expression	[9]
Prolargin (PRELP)	OT9EEBUJ	PRELP_HUMAN	Increases Expression	[9]
Spermine synthase (SMS)	OT8JYKNH	SPSY_HUMAN	Decreases Expression	[9]
C-X-C chemokine receptor type 4 (CXCR4)	OTUFSBX2	CXCR4_HUMAN	Decreases Expression	[9]
C-C motif chemokine 20 (CCL20)	OTUCJY4N	CCL20_HUMAN	Decreases Expression	[9]
Interferon-induced 35 kDa protein (IFI35)	OTV9RZ53	IN35_HUMAN	Decreases Expression	[9]
DNA-binding protein inhibitor ID-3 (ID3)	OTUULW5Z	ID3_HUMAN	Increases Expression	[9]
Tumor necrosis factor alpha-induced protein 2 (TNFAIP2)	OTRZH80H	TNAP2_HUMAN	Decreases Expression	[9]
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Increases Expression	[9]
Bone marrow stromal antigen 2 (BST2)	OTU4LCJV	BST2_HUMAN	Decreases Expression	[9]
EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1)	OTZVUOOB	FBLN3_HUMAN	Increases Expression	[9]
Neuronal membrane glycoprotein M6-b (GPM6B)	OT8Q1582	GPM6B_HUMAN	Increases Expression	[9]
Laminin subunit beta-3 (LAMB3)	OTFPU6W8	LAMB3_HUMAN	Decreases Expression	[9]
Nidogen-2 (NID2)	OTHC33FF	NID2_HUMAN	Increases Expression	[9]
Signal transducer and activator of transcription 4 (STAT4)	OTAK3VFR	STAT4_HUMAN	Decreases Expression	[9]
2'-5'-oligoadenylate synthase-like protein (OASL)	OTZ05YRP	OASL_HUMAN	Decreases Expression	[9]
Bcl-2-related protein A1 (BCL2A1)	OTWRYSNA	B2LA1_HUMAN	Decreases Expression	[9]
Lymphocyte antigen 6E (LY6E)	OTMG16BZ	LY6E_HUMAN	Decreases Expression	[9]
Interferon-induced protein 44-like (IFI44L)	OTXKORJP	IF44L_HUMAN	Decreases Expression	[9]
E3 ubiquitin-protein ligase RNF19B (RNF19B)	OTYCWKBP	RN19B_HUMAN	Decreases Expression	[9]
Amphoterin-induced protein 2 (AMIGO2)	OTPAIT1O	AMGO2_HUMAN	Decreases Expression	[9]
Probable E3 ubiquitin-protein ligase HERC6 (HERC6)	OT7G9PQE	HERC6_HUMAN	Decreases Expression	[9]
Equilibrative nucleobase transporter 1 (SLC43A3)	OTR60ZLA	S43A3_HUMAN	Decreases Expression	[9]
Interferon-induced protein 44 (IFI44)	OTOKSZVA	IFI44_HUMAN	Decreases Expression	[9]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Decreases Expression	[9]
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Decreases Expression	[9]
Type II iodothyronine deiodinase (DIO2)	OTGPNSLH	IOD2_HUMAN	Increases Expression	[9]
Interferon regulatory factor 7 (IRF7)	OTC1A2PQ	IRF7_HUMAN	Decreases Expression	[9]
Interferon-stimulated gene 20 kDa protein (ISG20)	OTCWRJJW	ISG20_HUMAN	Decreases Expression	[9]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Decreases Expression	[9]
Anthrax toxin receptor 1 (ANTXR1)	OT5W1GPC	ANTR1_HUMAN	Increases Expression	[9]
Interleukin-23 subunit alpha (IL23A)	OTYO99HC	IL23A_HUMAN	Decreases Expression	[9]
NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2)	OTK0PG7R	NUA4L_HUMAN	Decreases Expression	[9]
E3 ISG15--protein ligase HERC5 (HERC5)	OTZ5PR39	HERC5_HUMAN	Decreases Expression	[9]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[9]
Hypoxia-inducible lipid droplet-associated protein (HILPDA)	OTEID3ZM	HLPDA_HUMAN	Decreases Expression	[9]
2'-5'-oligoadenylate synthase 3 (OAS3)	OT6E5FYS	OAS3_HUMAN	Decreases Expression	[9]
Coagulation factor VIII (F8)	OTH6XHDU	FA8_HUMAN	Increases Expression	[10]
Myelin basic protein (MBP)	OTFZCEDB	MBP_HUMAN	Decreases Expression	[16]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Decreases Expression	[16]
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Decreases Activity	[17]
Tyrosine aminotransferase (TAT)	OT2CJ91O	ATTY_HUMAN	Increases ADR	[18]
Glucocorticoid receptor (NR3C1)	OTCI2YDI	GCR_HUMAN	Increases ADR	[18]
Thrombopoietin (THPO)	OTO73DZ2	TPO_HUMAN	Increases ADR	[18]
P-selectin (SELP)	OTWR90PK	LYAM3_HUMAN	Increases ADR	[18]

Indication(s) of Hydroxychloroquine

Disease Entry	ICD 11	Status	REF
Chronic renal failure	GB61.Z	Approved	[6]
Malaria	1F40-1F45	Approved	[7]
Plasmodium falciparum malaria	1F40	Approved	[6]
Plasmodium malariae malaria	N.A.	Approved	[6]
Plasmodium ovale malaria	N.A.	Approved	[6]
Systemic lupus erythematosus	4A40.0	Approved	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[8]
Colon cancer	2B90.Z	Investigative	[6]

Hydroxychloroquine Interacts with 4 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HUMAN pH-dependent viral fusion/replication (pH-DVF/R)	TTD16BI	N.A.	Inhibitor	[19]
HUMAN glycosylation of host receptor (GHR)	TTZGK1R	N.A.	Inhibitor	[19]
Toll-like receptor 7 (TLR7)	TTRJ1K4	TLR7_HUMAN	Antagonist	[20]
HUMAN toll-like receptor 7/9 signalling pathway (TLR7/9 pathway)	TT3A1EZ	N.A.	Inhibitor	[21]

Hydroxychloroquine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[22]

Hydroxychloroquine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[23]

Hydroxychloroquine Interacts with 30 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Decreases Activity	[24]
Interferon-induced protein with tetratricopeptide repeats 3 (IFIT3)	OTPGHZB9	IFIT3_HUMAN	Increases Expression	[25]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[26]
Serine/threonine-protein kinase/endoribonuclease IRE1 (ERN1)	OTY9R6FZ	ERN1_HUMAN	Increases Expression	[25]
Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1)	OT4TMERS	NFAC1_HUMAN	Affects Expression	[27]
Claudin-1 (CLDN1)	OT27KV99	CLD1_HUMAN	Increases Expression	[28]
Interferon beta (IFNB1)	OTYQGUB5	IFNB_HUMAN	Increases Expression	[25]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Increases Expression	[25]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Affects Expression	[29]
Alkaline phosphatase, tissue-nonspecific isozyme (ALPL)	OTG7J4BP	PPBT_HUMAN	Affects Expression	[29]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Phosphorylation	[25]
Cathepsin B (CTSB)	OTP9G5QB	CATB_HUMAN	Affects Localization	[30]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Decreases Expression	[31]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[32]
C-C motif chemokine 2 (CCL2)	OTAD2HEL	CCL2_HUMAN	Increases Expression	[32]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Degradation	[25]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[27]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[26]
Transcription factor p65 (RELA)	OTUJP9CN	TF65_HUMAN	Increases Expression	[25]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Activity	[30]
TNF receptor-associated factor 3 (TRAF3)	OT5TQBGV	TRAF3_HUMAN	Increases Expression	[25]
Nuclear factor of activated T-cells, cytoplasmic 2 (NFATC2)	OTK5T6HZ	NFAC2_HUMAN	Affects Localization	[27]
Sequestosome-1 (SQSTM1)	OTGY5D5J	SQSTM_HUMAN	Increases Expression	[33]
Interferon regulatory factor 3 (IRF3)	OT81U8ME	IRF3_HUMAN	Increases Phosphorylation	[25]
Occludin (OCLN)	OTSUTVWL	OCLN_HUMAN	Increases Expression	[28]
Mitochondrial antiviral-signaling protein (MAVS)	OTTQ0J64	MAVS_HUMAN	Increases Expression	[25]
S-adenosylmethionine-dependent nucleotide dehydratase RSAD2 (RSAD2)	OTCA9WCM	RSAD2_HUMAN	Increases Expression	[25]
Interferon-induced helicase C domain-containing protein 1 (IFIH1)	OTZA2AHA	IFIH1_HUMAN	Increases Expression	[25]
Toll-like receptor 9 (TLR9)	OTFZ45HX	TLR9_HUMAN	Decreases Expression	[34]
7-dehydrocholesterol reductase (DHCR7)	OTLILBUI	DHCR7_HUMAN	Affects Expression	[29]

References

• [1] ClinicalTrials.gov (NCT02444728) Cyclophosphamide and Hydroxychloroquine for Thrombocytopenia in SLE
• [2] Methylprednisolone FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] ClinicalTrials.gov (NCT04341038) Clinical Trial to Evaluate Methylprednisolone Pulses and Tacrolimus in Patients With COVID-19 Lung Injury
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7088).
• [6] Hydroxychloroquine FDA Label
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7198).
• [8] ClinicalTrials.gov (NCT04341727) Hydroxychloroquine,Hydroxychloroquine,Azithromycin in the Treatment of SARS CoV-2 Infection (WU352). U.S. National Institutes of Health.
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• [12] Secretory transport of methylprednisolone possibly mediated by P-glycoprotein in Caco-2 cells. Biol Pharm Bull. 2002 Mar;25(3):393-6.
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• [14] Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
• [15] Protective effect of methylprednisolone on paraquat-induced A549 cell cytotoxicity via induction of efflux transporter, P-glycoprotein expression. Toxicol Lett. 2012 Jan 25;208(2):101-7. doi: 10.1016/j.toxlet.2011.10.019. Epub 2011 Oct 31.
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• [19] Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
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• [21] Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):155-166.
• [22] MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol. 2013 Sep-Oct;31(5):779-87.
• [23] Hydroxychloroquine: a physiologically-based pharmacokinetic model in the context of cancer-related autophagy modulation. J Pharmacol Exp Ther. 2018 Jun;365(3):447-459.
• [24] Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M "Influence of hydroxychloroquine on the bioavailability of oral metoprolol." Br J Clin Pharmacol 49 (2000): 549-54. [PMID: 10848718]
• [25] Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery. J Interferon Cytokine Res. 2015 Mar;35(3):143-56. doi: 10.1089/jir.2014.0038. Epub 2014 Oct 16.
• [26] Hydroxychloroquine potentiates Fas-mediated apoptosis of rheumatoid synoviocytes. Clin Exp Immunol. 2006 Jun;144(3):503-11. doi: 10.1111/j.1365-2249.2006.03070.x.
• [27] Hydroxychloroquine inhibits CD154 expression in CD4(+) T lymphocytes of systemic lupus erythematosus through NFAT, but not STAT5, signaling. Arthritis Res Ther. 2017 Aug 9;19(1):183. doi: 10.1186/s13075-017-1393-y.
• [28] Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015 Jul;29(7):299-304. doi: 10.1002/jbt.21696. Epub 2015 Mar 9.
• [29] Hydroxychloroquine decreases human MSC-derived osteoblast differentiation and mineralization in vitro. J Cell Mol Med. 2018 Feb;22(2):873-882. doi: 10.1111/jcmm.13373. Epub 2017 Oct 3.
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• [32] Reactive oxygen species mediate chloroquine-induced expression of chemokines by human astroglial cells. Glia. 2004 Jul;47(1):9-20. doi: 10.1002/glia.20017.
• [33] d-galactose induces premature senescence of lens epithelial cells by disturbing autophagy flux and mitochondrial functions. Toxicol Lett. 2018 Jun 1;289:99-106. doi: 10.1016/j.toxlet.2018.02.001. Epub 2018 Feb 6.
• [34] Antagonist-mediated down-regulation of Toll-like receptors increases the prevalence of human papillomavirus infection in systemic lupus erythematosus. Arthritis Res Ther. 2012 Apr 18;14(2):R80. doi: 10.1186/ar3803.